THE EFFECT OF THYROXINE AND PARATHYROID EXTRACT ON THE wcmewca OF FLEXED TAILS IN A FLBXED TAILED STRAIN OF THE HOUSE mouse. :MUS MUSCULUSE Thesis for the Degree of M. S. MICHIGAN STATE COLLEGE Elden Edward Kline 1945 m armor OF mom: All!) PWOID mm W m “GIMME 01' many nus m A mm}: um mm 0! TEE HQ!“ W33 (1413 15986131118} by m xwm rm A THESIS Submitted to the Gram.“ School of Richlm Stats 00110:. of Agriculture ad Applied 861m“ in partial fulfilment of tho ”@1th for the degree of W O)‘ 30MB Mutant of Zoologr 19% m1. talk was dent undu- tho “IP10” and direction at Dr. 3. 8. Rant, Head of the Papa-mu of Zoning, maxim Stat. Gallop. hut halting. Indiana. Meledgnenh The mther 1e indebted to It. 3. 2. Rant. Deputeeat or “clog. for Me game help in giving count-active muck” end we- tlone. to Dr. J. :l'. Moe. Depart-eat of Hueieky end 13'. w. I). Baton. Depart-lent of Kathmuoe fer conned. Aemovledpeet mt elee be given to George 3. Jet. III-tee !. Oetenson and P. A. Rankine for “spinach and Moe. 1. 2- It. 6. 7.. a. 9. 10. 11. 12. table of data“ Emmett» meter: nethode Breeding Pregn- Material central. Theory and ObJeeuve of “nut-011m mutation Incidence of Heme 1n Murine Emeflmte Theory and GbJeotive of the Parathyroid Experiment! lacunae of nemre in the Parathyroid Experlneate memeelon Bibliography ‘_ _ 1.1;- _.__A___‘. _.. Inflammation fie purpose of this hmtigation woe to newton the effect of this-Orin. and parathyroid enact on tho fleme to the m1 of e flexed tailed. etrdn of nice. It was eoneidpred poeelble mu theee hormones mm: 3!!th the lucid.“ of flexed. an. in the ofteprlns of parent stock Iron a flexed “fled “rain. M problene were etudied: (1) the effect of mreeeed. neu- house mama to thyroxine gum-tram: on the inouenoe or an. are; and (2) nexus-e being partly a bone anomaly. 1t wee dun-able to inveetigete the often of puatbymia extract on Home once thie hormone to eo intimately concerned um: ninerel ”woollen. Thie investigation nae conducted at the rodent colon: of the Doparmt of, Zoology at Mom“: State college. Hie-ion K A. {leach-toil “rein of the house moo (Hue moulne) wee devel- oped by Dr. B. 3. hot who dieoovered the reoeeeive gene utetioa in 1927 in e new: of albino nice. the abnormal enimele are one-10 at birth and We, rigid mm... o: the tail. any individual .1» show 3 thite hell: spot (Clerk. 19331). mend—toil ie ohceoterieei by etiff. angular bench or epirele. or by rigid «pate vithout neuron. rho oharaoter ie very urleble. eome taile “in: extremely heat while a. fee homozygoue individnele can only he dietingniehed from morale by 'hreeding teete. Hut end rerw (1928) found. the character on e reeeeeive but gave e ratio of 6.9 norale to 1.0 flexed tail in the )2. hot. Hi:- ter and Per-er (1933) obtained #008 I 1.12'per out of flexed-toiled nice in a, beam... In an effort who may with poetnetel differen- tiel death rote, only unclepletei littore of seven or more eninele were the: need. as these littere the peroontoge o! flexed-toiled nioe wee 338.30 1 1.72. which is fairly cloee to the expected 50 per cent for the Memes. implying the use method to their 1’2 data. they in- oreeeed the percentage of flexed nice from 15.17 3 .68 to 18.66 3 1.6! per out (25 Per out expected). Norm). overlap are phuovpioally norm]. individnele which ere homozygous for the flexed or belly epot gene. Clerk (193”) den:- etreted that both the hell: epot end flexed tail typee hei e high per- outage or moral ever-lope. ehile anemia behaved ee e. typieel nucleus!» recessive without normal overlepping. This home]. overlapping of the nested character hoe been reported by moat inveetigetore. Belly epot me than to be very oloeel: linked. with the flexedpteil-enelio oonplex. 'tenenoff'e cleeeioel work (1935) olenrly deeonetretethho neohenn ion of tail fienre. The flexnreo oonsietod of uileterei fooione of edJecent vertebrae. If tneien were complete. otreight etifr eeenente were produced. The immediate ounce of the meion wee feilnre of early cartilage in part of the invertebrel disc to differutieto nomelly into fibere about the fourteenth do: of embryonic lite elong'eith en epperont reduction in the nnnboro of cello in the ehnoreel region (e retardation of growth). it period.of flernre ecoording to Kelenoff the early cartilage peripherel to the nucleon pnlpoeio ie differen- tiating in the nor-ole into fibrous tissue by flattening end elonga- tion of the cello together with o rapid multiplication in the lumber of cello per unit volume. fibere the flernre occnro thie ditferenti» etion ie eon only on one eido. L been! in the notoohord wee often coon but wee not the ounce of the foeione. Two possibilitiee were diooneeod by Xenenoff no to how the zone caneoe toil flexnree and.e~ nemio. me io that anemic we produced by the one rotor-action in youth which produce the flexeree. The other ie thet onenie eppeero earlier than the flexing and produces the more genernl retardation evident to the eeeller length of the vertebrae. mono“ nsguted tho anemic wee owed poeeibly by e retardation of growth in o heele- poietio center ouch on the liver. This who supported hr the prelimi- nary study of indereon (1932) end.leter in his own inrootigntione Emmott found anemia was due to a delay in the liver cum-amine. Emmi! (1935.) found the node together with the flexed toil condition in the embryo no early on fourteen daye otter fortilieetion. thin in before the bone narrow*eeeunee e.hneaopoiotio function. ehioh ie placed ct the oixteenth do: by De Abel-lo (1927). hunter end not (1933) denonotreted the treneitory ochre of the anemic which dioeppeered Ming the firot few Me of life. hey found the nee-born individnnle to be. on the average. deficient in the hono- globin end erythrocytee. Gmeberg (191m). (191m) deecribed the one-o nie no nornoqtic hypoohronio oneeio. pereioting during the firet two weeko after birth. but having ceeeed at the beginning of we third week. Pathological cello enrvive in the circulation for at lenet two. ht not more that eix weeks after birth. an the diooppeerenee of thee-e enrviving cello the red blood picture of flexed nice becene normal. itixter and me (1933). Kenenoff (1935) end Grcneberg (1912) have found that adult flexed nice. following recovery. have blood cell connte ct lecot no hid: or mater than normal. In a letter publication. Grenoberg (19142) found adnlt lice chewing on enonoly of red blood cello. 'i'hie wee canned by peroietuoo of cone eiderooyteo into adult life. Otherwioe he found the blood picture quite normal. Bideroeytee are red cello of onenioo containing oonoidoreble cnounte of free or eoeily detached iron. theee are not confined to onenioo. hey have been found in normal embryonic rate and nice. in human embryos and new-born babiee. These eiderooytee. which are haemo- globin deficiente. were the buie for the anemia he new cello 'eidoro- oyte aneuia.‘ which to diotinct from all other known choline. hone oidorocytee were found 12 deye before birth. 1‘2 generation and baacrooeeo node by Hunt end Perner (1928). Hunt. Hitter end Pennr (1933). Xamenoff (1935) end Clerk (1933) pro- duced e eiaifioent deficiency-of flexed-toiled nice. Anonie heo been uggeoted no the dicgootio character rather thm flexed or belly opot. Kenonoff (1935) udeevored to chow that the deficiency of the floxodp tail close in the backoroeo wee due to faulty olaooifiontion rather than differentiel prenatal mortality. for only 13 per cent prenetel mortality one found in flexed-toiled nice no compared eith 31: per cont by Meatball (1921‘) in non-flexed. MacDowell'e figure. homer. includoo all mortality up to weaning time. Clerk’o (19374) and Omen- berg'e (19%) nor: etrongly enggeeted the enemio io e acre conetent and dependable expreoelon of the flexed gene than ie the flexed tell itoelf. . . . Hunt. out» and Permr (1933) noted together aninelo with the cane type of flexure to see if the various degeee of flernre were controlled by genetic fectere. they eere unable to develop pure lineo of flexed animlo because of eterility due to inbreeding. They found the coefficient of correlation between and" of flexnreo in flexed parents and their offopring m +.2It3 :1 .029. which 1. e olight um. ficent correlation indicating that the degree of flexure is inherited to some extent. Reporte of tail mutatione in nice eimllar to the flexed-toiled otrein of Hunt'o have not been uncommon. Plate (1910) doeoribed e kinky tell mtetion end concluded that its inheritance did not follow Mendelian love. in extenoire etudy of the hietology of Plete‘e Intent nice one node by Blank (1916). Glueckeohn-Sohoonheiner (1938) in otudying the develcpoent of two toilleee mtente in the nouee. found the teile become conotricted on the proximal aid. roenlting in necroeio and reeboorption of the toil diotnl to the oonotriction. He ouggooted n dieturbence in the early embryonic development. Both Plete'e and Gluedteohn‘e orplenetionc resemble the 14.. presented by Ianenoff that the abnormality of Hunt‘o flexedptailed otrein was due to an interference in the early general metabolism of the embryo. m. Gluttoohn-ddionheieer end Bwoon (1930) rqcrted e toil notation ohioh one virtually e lethal dominant. in the heteroermo ' otete there were either ehert teile or no toile et ell. Often ehortoned or crooked epinee and e lettered viability after birth were reported in connection vith hie notation. Detrovclekeie-Zovedekcio (l927e. 1927b. l928e. 1928b) end hbrorol. thin-hm end tobooioff (1927.. 1927b. 1923. 1930a. 1930b) dee- a'ibed a notation in the honee notice reoolting in partial or coqlete ebeence of the toil end in mine flerureo end conetrictione of the toil rement noonntered in x-rey experimto. i‘hie treit thet Dobro. voloknie-Zevedehio (1933) proved to be e aniline-t lethal no with rerione flemee nodifying geneo wee ieoleted by oeleotion into oppor- nte otrnino by weloey and Mn (1936) (1937). n einiler character preeonted by Casperi and fluid (19110) con- oieted of kinky teile end ebnornelitiee in the beckbone end ribo. It behaved like on nteeonel doninent with high or complete lethelity in the honome condition. A short-toiled mutant in the house nonee reported by melee: (1935) was lethal in the homeymne otete. Evidence one found in en enbrye- logicel otndy that the normal development of the nurnl taboo one. in part. dependent on the preoence of :1 normal notochord. Reed (1937) deecribod the inheritance and expreooion of a tail mutation. mood. inch reoponded no a. dominnnt. in 1931 Crew and incl-beck reported e tell abnormlity 'Pis-teil' in the houee nouoo. Ehio cherector closely reeunhlee the flexedpteil etrein of Hunt'o. ”Pig-tell“ ie dne to e. receeeire gene with nodifiere and some intrauterine condition effecting ite penetration in the hone. qgteo. flexed-tell m detox-thee w neute- and late (19$) in threaten; micaletng (deer none) no e. genetic reoeeoire. !he use expreeoed iteelf in e ehertoing end dietortion of the (caudal vertebrae with dio- ‘brtion of the invertebrnl Joint. Ioenee end flecibeell (1932) reported e not toil nation. 'lcrer- my in the hem mm. ‘ I ”Stub. e Intetion. wee rmrted by Mn and Quentin-Minor (191’2). more ree e. reaction of the tail to e ohort otiff otnb. It noted an o. reoeoeive ehoein; e greet uniformity of ell mtento. By thie nrverene con reodilr oee tail notetione ore not Income. but few have the edventepe feond in the flexed tell etrein of ht‘e . there nah voluhle reoeerch hoe elrecdy been eccoqliehed. Methods i‘he oninole were kept in ohoet metal cages. twelve inchee own and deep provided with n wire nooh top. Wood ethingo were need no litter in the cegee. Water wee eupplied by grevity flow alone bottlee and taboo. the diet of the nice we relatively ccnotent. coneieting of a mod feed of mixed greine and coeds fed in pcrcelein «more. and dog biecnito enoponded by a wire from the top of the once. Iced and water were constantly eupplied. Sanitation coneieted of weekly re- newing the wood eheving litter. washing the waterobottleo end taboo and replacing clean. dry porcelein diohee for the feed. The caeeo were thorouglly washed end dried once a month. The tenperahn'o wee held conetant at eighty deg'eeo rahrenheit by e thorn-octet regulation of the steam heating mien. be building one new. node of count blocks with concrete floore. a deeirable and efficient place to work. fine otatietioe need to interpret the remlte obtained in the emeri— nente «played comcn end etendnrd statistical nethode. me etuderd error of e percentage was obtained free the following statistical formic where the m of P and 0, ie one hundred per cent. not- fqm s. 3.3% - Standard me:- of a deciml fmtion. P I The 'frectien of the nice touch are not flexed. Q t; 14’ O The fraction of nice that are flexed. h e The total number of individuals need in calculating 9 end t. we otondnrd error of e difference was calculated from the formula. s. 2. diff. - [(e :1)?! t (a 1122)2 s. 3. diff. I; who etmdnrd error of the difference between two decimal fraction», 8. 3.1 :- Standard error of one decimal traction. 3. 3.2 I; Studerd error of another decimal fraction. The 't' 'velne wee found. free the female: in P1”? P1 I he fraction of flexed in one may. 1‘2 I the fraction of flexed in another group. 3. It diff. . Stead-rd error of the aiffereeoe. me odde were otteiaed free the'reblee of Peereon'e me In ltmotiee'I he leivere (1930). Breeding i’ro gram All the nice need no psi-at stock were numbered serially. allow- ing no (biplioetee. the numbering wee accorapliehed by reacting toes. The removal of tees cmeed no noticeable inconvenience. One male nine). wee pieced in e breeding cage with one to fen:- fe- nclee. When the females cane into advanced pregnancy. they were remved end placed in individual cases. where the young were born. Observations were mde daily until parturition. The newt-born nice were individually recorded as to number. sex. teil flows and date of birth. After the first day the new-born nice were obeemd and recorded weekly for et least three weeks. or longer if the flexure could not be definitely determined. ' The female wee refined to the some breeding use end ‘eele 21 days after parturition. Each female was nlweye mated to the name hole for the antral end experimtel litters. to keep the control and experi- mental coupe es genetically elite no possible. Homozygous, flexed females were elweye crossed with homwyns flexed nnlee (flexed x flexed) no that ell the progeny were homq'gons for flexed. {me first litterfifron eeoh female was recorded as the control Whinintered dininfllhueetetion. rhe W the _ tntion eried the f e received mW 2 my aid. extrnoto A eyeten of electrifying the degree (grade) of flexnre wee need to designate by e number the amount of tail involvement produced by the expression of the flexed gate. The method need wee e nodifioetion of Hunt. Minter end Permr'e (1933) classification. 10 Like these writers the ewe fundamental characteristic» were need: (1) the percentage of the tail length which was rigid end (2) the number and mlme of the angles. i'he object was to grade the wt of tail internment. The male was as follows! Grade 0. Eon-flexed and cannot be differentisted from n nornel tail. By visual inspection and digtel examination no fused vertebrae could be detected. Grade 1. lon-flened. e streight tail with sons fused vertebrae. This path could not be dietinqnished from a. normal tell by visual on. eninntion end sometimes only with difficulty could the {need vertebrae be found by palpation. Palpetion consisted in steeping the base of the toil es close to the body as possible betveen the timnb and forefinger. then. bending the tail at about a sixty degree angle. the fingers were noved toward the distal end of the tail. ellowing the tail to bend end slide over the end of the forefinger. By this method fusion involving only e few vertebrae could be detected. Grade 2. Re, or nlncst no. visible flame. A. slight enlerge- ment could be discerned in n few. Digital examination easily reveels e. fusion incorporating several vertebrae in e. straight stiff semi. There an be care than one group of vertebrae involved. Grade 3. diameter-ind by one scene-defined i'lexure in the tail. more also may be one or more etiff. straight portions. Grade ‘1. M or more pronounced flemree of the toil. Grade 5. heme names the form of e. spiral ’cork-ecrew tell" (amt). ran involvement or the severest type. consisting of several bends. extensive vertebral fusion and decided shortening of the totel tell length. In smiling the tall: for new: in the control group. mum]. can were pineal 1n the non-£10106. cateipry. Doubtful can» in the treated ozporimtal mpakvm placed in the {loud group. Error. in classifiéauon thus rodnom the difference batman the two papal» none. -In sf)!" of this procedure real difference. batman the Mrs groups were obtained. Katerial A flexed-tailed ctr-din of the house mouse. 53 momma, we: obtained Iron Dr. H. E. Hunt in March. 1910. m nice were direct deeeendante of math flexed-tailed strain recovered from the numeroue outeroeeoe performed by 3!. Hunt to insure a vigorous flexed-tailed breeding stock. In order to obtain sufficient numbers of breeding animals the mice were chosen and bred with no reference to the degree of {lean-e. mus. e11 mietione 1n the degree of flame were need. but no ant- ml: were bred unless they demonstrated e definite an involvuent. Became of the low viability of the flexed-tailed nice. inbreeding was not need. (Hunt. Mixter. end farmer. 1933). the aloe me prob- ably 111311: heterozygous for gnu other than flexed. finch inure-med the difficulty in obtaining mm and manly dytticent reenlte. ee- peoielly in at e character an the degree of Home. BUMBI’IBS 0F EXPEPJMEII’EL MICE Controls Control One Thyrozine control Parathyroid Control To to}. Control: Thyroxlne Thyroxlne .0015 Thyroxine .0025 Thyroxine .0050 Thyroxine .0050 «- 7 dean Total Thyroxine - Experimental (All Dilutions) Parathyroid Parathyroid 2 units Parathyroid 5 units Total Parathyroid zxpermental Total number of individuals TABLE I 335 208 671 77 3? 1% 360 86 136 671 360 1167 13 controle A control group deeimted no “control we.“ were offepring vhoee perente were never need in my experimental capacity except to reiee e ember of control littere. three hundred thirty-one offspring were prom of ehioh 5 were non-flexed. This is 1.18 per cent non—flexed and 95.51 2 .6; fumed. Rice Dorothy Porno! (1928) in a study of the inheritance of flexed» tail. bred fonrten peire of flexed eninele. flioh prohced 127 young. all flexed. Bneeell Hitter (1930) croeeed flexed with flexed. comr- ing 578 flexed (99$) and 6 non-flexed (1% 1 mm). In this work the tiret litter from each female one o. control. on: during the geetotion of enheeqnent litters tron the eene females ' were the her-once eduinietered. The thyroxine control may one eonpoeed of the tint litter from the tenelee who received thyroxine insectione in the following littere. No thyrexine wee edninietered daring the geetetion of the thyroxine control group. no thrroxine control numbered 205 mammal. of when Mn 2 $853 vere neon-flexed. The perethmid control poop was composed of the tiret littere iron the {melee who received parathyroid inJootione in the abutment littere. he pernthyroid antral group mnprind 121 offspring; of then three were non-flexed. or 2.80 1 1. :3. on. group hot! n higna‘ pcmtage of non-flexed than any other control group. the dittereneee hetvem there control we. in the inddenoe ef flexed toil. were ell due to meme. no the following etetleticnl facts ehoe. rho 't' value in comparing the parathyroid controls with the Manual One' group one 1h 0.88. If the odde against the chance causation of e. difference are small. the odds M2: its being date to {finance are large. The odds are 1.532.. to 1.00 against this difference being due to anything but dunes. The 't" value for the difference between Pam's and the parathyroid. contml is 1.23. Here the odds are 3.59 to 1.00 ngainet the occurrence of a. chance deviation as: gran. no or greater than the one obtained. In cowering Mixter’o date with the parathyroid controle. the “1:“ value was found to be 0.38 and the odds are 2.38 to 1.00 that this was due to chance. mo ”1:“ value: for the thyroxine controle and parathyroid control ie OAS and the odds are 1.70 to 1.00. All there telnee for 't" ere well below Vela“ indenting sini- fioant difference: and thie ie true of the parathyroid control: no well no others. The control we ere. threfore. eemtielly alike with reaped: to the incidence of flexed. indivirhmle. Control Gna #336 Permar 127 Hixter 578 Thyroxine cont. 208 Para. Gonte 127 TABLE II cozmois Percent flexed 98.51 1 00.60 100.00 2 00.00 04 99.00 00.101: 99.52 t 00.h8 97.20 1’ 01.16 't' value when com-- pared with the para- thyroid control for the differ- cnoe O. 88 1.23 0.38 0A8 Odde against the occurrence of 0. chance dif- ference when com- pared with the parathyroid con- trol as great as or greater than the decimated on.e 1.6h81 3-5931 2.38:1 1.10:1 PERCENTAGE OF NON-FLEXED IN THE CONTROL GROUPS I. CONTRG. ONE 2. PERM AR (I928) 3. MIXTER “930) 4. THYROXINE CONTROL 5.PARATHYROID CONTROL PERCENT 3.0- 2.0. LO. . ooL—Z FEE—.5 FIGURE I 15 beer: md Objective of fluorine Administration Disturbance in the rate of growth can produce ehornelitiee. Stocknrd (1921) by stopping the develoPmmt of landmine urbane. pro- duced n greater number of ebnornelitiee than in the controls. It wee only at certain critical tinee that the ahaornal embryos were produced. mama:- (1932) in at study of the creeper fowl reported that slowing down of growth effected the development. Kenmoff (1935) postulates that two things no: necessary for production of ehormlitioe by modification of the growth rate: first. a. slowing dam er stoppage of growth whid: may damage the rein- tive rates of growth, and eeoond. e critical point in Melopnent which is usually e period ef rapid growth. These two conditions he fomd in the Heady-tailed muee- First. the slowing of the growth rate had occurred eons time before the thirteenth day; eemnd. the vero tebrnl calm woe etill growing rapidly at the thirteenth day. In a. careful embryological investigation of the flexed-tail strain. Kmoff found that until the thirteenth day the development was ap- perently normal. On the fourteenth and fifteenth den he observed that the cells on the choral eide of the developing vertebra did not divide as fast es the normal. indicating a. slower cell neteboliu. That this was not nerely s local manifestation we! wanted by the constant shorter lmgth of the proximal caudal. and probgbly e11. vet- tebrae. Thie shorter law my be due to reduced rate of neeehchymal cell division ef the emtrs enlsge in the early developmental stagee. ‘rhe total neither of cells per unit volume was the some in flexed end normaletniled nice. so the difference was undoubtedly due to the rete of cell division. This difference in also in clurly visible at the thirtemth any. 16 the foetus was noted to be quite ohmic et fourteen days. Vhether the anemic is the primary cause of the retarded growth resulting in look of differentiation of the tail vertebrae. or ehether the reterdn- tion of meth u e canoe of the anemia and the feilure of the m... of the intervertehrel discs to differmtiote. is undetermined. In either once. the anther endeavored to combat the reterdetion of growth and develop normal tails in the flexed-toil strein. his wee done by trying to increase the utehelisn of the fetus by injections of the thyroid hormone. thyroxine. into the mother. m: the thyroid he the capacity to increase netebolisn and growth rete ha been sheen by many investigators. A synthetic thyroxinc was obtained from Roche-Drama. lnc.. Nutla', How Jersey. Three dilutions were administered: 0.0050 up; 0.0025 can. and 0.0015 ngns. to each female parent daily. lhe admin- ietretion was begun at leest five days before the feeelee were placed with the sales to be bred. and continued through gestation until peroxi- ticn. i'he mount of solution injected was 0.2 cc. enhcuteneonely for ell dilutions to nininise and keep constant any effect due to quentity of the dilutingeolution. The amount of thyroxine see erbitrnrily deterrined. the object being to give e sufficient! a... It was found that in the group of mothers receiving the largest enount of thyroxine. five out of ten died and no doubt others would econ have followed if the injections had been continued. The surviving females were subjected to e. lower dilution and had normal gestetions. l‘o another group of nethere thyroxine at the level of 0.0050 nan. daily use ndninietered for e period of seven days only. his period was to begin four days after noting. the indections covered e period 17 of gestation free the fourth to the twelfth day. fhe date of eating was obtained by daily examination of each female in the breeding cages for s vaginal plug. When this one found, the female was ioolated and thyrexine injections began on the fourth day of isolation. She object of the deviations from the preceding eminent was to administer no adequate ass of thyrozine for the fetus without kil- ling the mother. The dose of 0.0050 mgms. per day. administered for a period of sixteen days was found in previous experiments to produce severe cachssie. and in some instances death. By the adoinistrstion of large doses for a short period it was hoped to incrense the netshcl. ion of the fetuses at the critical time. but to stop the adlinistrstion before the mothers became emaciated md failed. to produce young. The injections were not carried beyond the twelfth day of foetal development because Kenmoff‘s observations eugeeted that flsnre is due to a lowered notebelism sntsdating this day. It was sensed that the ties to prevent retarded north was before it had hem. 13 Incidence of home in the i’hyrozine Ecperinmte fie thyroxine control litters were ecneidered e corps-site control mop for comparing with litters borne by thy-ruins treated mothers in all the experiments. involving the three dilutions of thy‘rcxine. £113 is justifiable for the first 11th of each female was e control litter (thyrozine oontrole): the second. third or fourth litters sore borne after the tensile had received Wroxine injection. eon. e! theee fermion had received differmt doses previous to the birth of diffemt litters. Iron 33 thyroxine control litters. 208 eflspring eere obtained. me nonwflexed teil was found. constituting 0&8 3 0.“ per cent of the population. The 'Gontrol the" group is composed of the offspring of those authors were never need in any experimtal capacity except to raise a. number of control litters. The group of females receiving Wroxine at the level of 0.0015 me. daily. promoted TI flexed progeny {100 per cent tiered). fie mothers receiving the thyroxine dose of 0.0025 ngne. per do: had 98 offspring. of which 2 were hem-flexed (2.0“ 1 1.33 per omit). The group having thyroxine ministered, for several days st 0.005. and later at .0025 we. per day. had 37 flexed offspring (100 per cent flexed). file group receiving thyroxine at the level or 0.0050 me. for seven days only. produced 1”! progeny with 2 non-flexed. or 1.37 3 0.95 per cart non—flexed. ill the offspring whose others received thyroxins in some dilu- tion were combined into one group. termed “thyroxine-ell dilutiens.‘ which had a. total of 360 progeny. Four of these we non-tiered. or 19 he poroontogo of non-nond m oboorvod to to 0 por coat is tho mo roeotvtng .0015 mo. and .0050 mo. daily; thio 1o moo tho control may. B10 groupo rooolving thyroxino at tho 1on1 of 0.0025 mo. 6.9.11: and .0050 IQ. for I dun had roopootiroly 2.03 3 1J1} por out and 1.31 2 0.95 por out non-noxod. he” voro both hlfior than tho thyroxino oontrolo. By cannon statistical muoio thooo dutoronooo were not found olplnoont. To oomtoln vhothu' m of tho thyroid” oxporinontol ponpo had o. oigiflcant difforonoo tho 't' value was ooqmtod for tho dittoronco bottom oaoh oxporiuntal group and tho thyroxho control mop. (m1. 1') ho 't' ulno for tho thwroxlno control couporod to group “control Ono“ to 1.2!}. no o’ddo ogainot this difforomoo bong duo to anything but ohanoo oro 3.67 to 1.00. thou no the groatoot odd: found in tho thyroxino export-onto. myroxino oontrolo oonporod to tho group thyroxino 0.0015 boo a 't" nine of 1.00. The oddo against this ditforuoobotng duo to woo aro 2.16 to 1.00. no 't' who when oomtod for tho difforoooo botvoon tho thyroztno 0.0025 group and tho thyroxino control m 1: 1.0!}. {ho oddo oro 2.35 to 1.00 undo-t tho dlrforonoo toms duo to ohmoo. filo thyroxlno 0.0050 group oomarod to tho thmmo control group has a '1' mo. of 2.16 to 1.00 and tho oddo m 2.16 to 1.00 must the difforuoo Doing duo to ohmoo. Thou figuroo aro not ototiottcany oigniflcant. A 't' voluo to ho statistically omittoont boo o voluo of 2.5 or abovo. Tho oddo onloot any number bolov 21 1: usually not considered otottotioolly otpinoant. In «moths tho thyroflno control map to tho thyrozino 0.0050 for 1 duo tho 't' voluo to 0.83. When the control group 1o oonpand 20 to tho coupooito map. thyroxino—ooll dilution. tho I't" vulno io 0.87. hr both thoso two lottor groups tho oddo oro 1.06 to 1.00 and 1.60 to 1.00 than any dirforonoo would be duo to anything but chonco. Added oviduoo that thou voro not oigificont difforoncoo no oboomd by noting the pcrcontago‘ of nonnfloxod in othor control littoro. Group u(Bantu-01 Ono'o" porcontngo of non-floxod individual. is 1.119 1 0.66. which 1. about tho cm as the 1.37 3 0.95 per coat of non—floxod in tho progeny of tho twrozdno group which roooivod 0.0050 man. {or oovon doyo. rho parathyrold control group poooooo 3 non—flout 1m. 1. 2.30 t 1.02 per cunt. which woo mam thou any thyroxino group. oithor control or oxporincntol. The dog“ (undo) of tail flcmro m shown by Hunt (1933) and other: to ho inherited to come cxtcnt. In our oxporiunto no otfort was mdo to note nioo with the came dog-rec of tail floxnro. Tho pnronto' orange dog-coo of nomro vcro nootly in olooooo throo and tour. but individuals in all classes were nood oxoopt 01o.» 0. (tiara VIII) The distributions of dcyooo of flowo in tho offoprin; voro max tho can no in tho paronto. (chart 1!!) Tho offspring in general difforod only from tho pox-onto in that tho oxtro-oo. Glooo 0 and Clnco 5 oontninod highor porocutagco of individuclo .011; the otfapring. which to due to tho «common of gonoo modifying tho 410509 of flomro. It in hotifinblo to conclndo that thoro woo no offoct on tho incidenco of floxod tail in tho progeny from homggono notingo of Hunt's flexed-toiled otroin by tho administtntion of thyroxino to tho pregxant tomoloo undo: the conditions of thooo oxporinonto. .3353 24 0503.030 .500 ~ - omoo. oqnxophga 800. @520?“ mmoo. mqoxoaana mfloo. 000000000 one Hopunco 3.38 .3800 3.2.. 3 .3 00.00” 00.3 8.8” $.00 mm.mm eoxoau anoouom 3.00 a .338 3.00 n RAo 00.00 H 00.00 9.8 n no.8 8.8 a 8.8 8.8 a 9.8 3.00 a 03.00 conoauaaon auuonom meNomwma mun manqa N o m o m H uouoauuooo nopaum 0mm 0.: R 00 2 HR 5m eoxoao hopaum 0% mi R mm 2. 0mm mom H0908 uaada Huom.H H60.” H.mfi.m :30 H.mn.m H.~m.m 88% “:5 05.0 shad 3 08.0 @500. .000 0o000Mw000 00» non» unuooam no anon» on acapwdbod a no 0000900000 .5 330...... .80 5.0 3.0 co.“ :0; 8." gm...“ 35; o» o HHm~.0 50 2n 0500 .0 030 .0 2.000 .0 mam.o 30600.33 05 no nouua_0hxvnmam azHMomHma bu HHMda .8332. do .mfl. omoo. :3 S .20 omoo. mmoo. .30 500. .20 26 .28 .0? on? .0? on). 0" .UP .28 .08 .28 .38 .28 .008 THYROXINE PERCENT NON-FLEXED l. THYROXINE CONTROL 2-CONTROL ONE lTHYROXINE .0050 4. THYROXINE .0025 5. THYROXINE .00l5 6.THYROXINE .0050 (7 DAYS) 7. THYROXINE ALLDILUTIONS PERCENT z. — F‘— l.O-- I l L o jag- 3.14.... [7 WI EACH GRADUATION EQUALS TEN ANIMALS FIGURE ll THYROXINE DEGREE OF FLEXURE IN THE OFFSPRING THYROXINE CONTROL —- THYROXINE .OOI5 “"“‘ THYROXINE .0025 W THYROXINE .0050 M THYROXINE .OOSO ’ W PERCENT 4‘ "W” 50.. 4o \ IO or“ A .. 0 0 I 2 3 4 , 5 DEGREE OF FLEXORE FIGURE Ill 21 men: end Obseottvo of tho Parathyroid menu-st rho home of the parethno 1d gland 'parothemne' rennet" «1.. ohm and phoephete “tubal“: 1n the body. A detioioncy been the col- ohm level of me plasma and flow. If the 10701 tone low enough, tetany romlte. Injection of the hormone result in moth: and nor-s mo sedation. Parathyroid hormno lower: the giro-photo lml and with. drawn calolun hon tram 3011.. Ne intimate oonnootion uth calcium metabollu meted its use for this expert-eat. The parethyroid preparation was obtained from rorke. Date and Oompony. Detroit. max“. no trade name was “PeroiunJ M cubic actuator oonteinod one hundred units. Eho mt. inject“! into the mice were two and. the units. diluted with sterile water on that eech eubmtanooue injection totaled 0.2 co. the solution we teeted for pH with I'Bitreuine popor' (B. 3. 8mm: and Sons. How York) and broad“ to pH 7.9 with coal“ oarbonato. men tho pH was not adjust-d. eterile momma-on: emcee: fomd at the point of injection. when odJueted there you no difficultlee. file firet 11th:- morded from 3 “ml. served. an e control utter. The mothers of tho loco-um; um" received. the utnot. the 111300. tions or the extract began tvo due after the females vere put into the breeding oagoe with the male end continued until the birth of the offspring. he fondue ver- ioolatod. from tho also as soon a: they we" obumd to to pregamt. me bongo use orbital-11: bond on the muted don for tho dog coloniatod by tho anwel'e vetflt. 22 Incidence of norm-e in tho Punting-mm leperiunte mo offspring in the parathyroid control mop numbered. 12?. of whia 3 were non-flexed or 2.80 3 1.1I6 per cent. on. m e hiw percentage than in an: other control group. The offspring whoee per- ente rocoivoi too units of prethyroid oxtroot per our moored 86; o! thooo 11 were non-flexed or 12.79 3 3.60 per cent. Hon-flexed off. spring appeared h.57 more tinee in those littere than in the littere of the parathyroid control coup. and 8.58 time more often then in the littoro of new control One. ie the parathyroid control group had. tho higheet percentage of non-flexed. iodivichnle of en: control group and toe the logical om- trol. the 't' value were dorived by common otatietical nothodo from emporium: of the data of the parathyroid oontrole with the data from those. offspring who” paronte roceivod parathyroid extract. no 't“ velno of the pmthyroid group receiving tvo mite daily than compared with the parathyroid control group wee 2.57. i'hie ie a oimificant difference. Among on 50 offspring ehoeo mother-e received five unite of pore- thyroid extract any. there were !onr non-flexed. or 3.00 2 3.30 per coat. The non-flexed indiviaele vore 5.3? time more prevelent than in the. group. “Control Qu.’ and 2.86 times more moot-one than in the parathyroid control map. file 't' value for thie group en (mi to to 1.27. on. group ie then not eigificantl: different fro- the pore—- thyroid oontrole. rho parethnoid maps of five unite and too unite per dew were compared etetietiooliy. ie there no no eigifioent urns...» bottled the two we the oon’oinetion eee valid. me 't" velue m 0.91. The combined data of progeny wee porente received either too or fire mite 23 of perethyroid daily. total 136 offspring. fifteen were non-flexed. repreeenting 11.03 per cent. on. 't' value of thie combined group no egoinet the parathyroid contrcle was 2.69. hie ie eialificent. be odde haunt this happening again by chmoe were lhl.85 to 1.00. i'he odde mu the occurrence of e deviation eo greet no or greater than the dioimted are 99.00 to 1.00 for the parathyroid group of tee unite and 3.90 to 1.00 for the parathyroid group oi’ five unite mu. ’ Stetietineliy. the effect of parathyroid oxtrent on the incidence of flexnre in the flexed-tailed etrein of Hunt’e wee eipii’icent. 'i'he deg-«e (green) at flexnre in the pmthymid conbined group. too and five unite. had 0. higler repreeutetion in the (rodeo eoro end one ad an apparent rednetion.in the other extr-ee. credo! four and five. on. devietion iron the parathyroid oontrole. ee eon in i'able Y1. wee eleo obeerved men plotted with other coupe in figure Y1. This difference was again ehcen in figure 11! ehere the overuse deyee of flew-e of the penthyroid combined group. teo end five units. woe oleerl: shown below that of ite oontrole end on other coup. The degree of ilerure of the offqaring when wagered to the porente of the parathyroid groupe is show in Figure 11. hr the off- epring grade eero is possibly higher while grade 5 ea: be lower than one would expect in randon bred population. H0 conclueion can be dream concerning the effect of pernthyroid extract on the grade of flame bemoe of the shell number available for thie etmh. In oheerving Tablee 7 end 11 e. discrepancy ie found in the per— contep of non-flexed individnele in the parathyroid combined gronpe. The percentage (15 per cent) on |table 71 ie greeter than the percentage (11.03 per cent) on Table 7. he date from mid: the percentage were 21: obtained in i‘eble V repremt e fraction of the deto in i'eblo VI. ihio dieoropeno: ie be to the feet that not oil the indiviaele each were obeorvod for being flonod or eon-flored were recorded an to the degree (node) of floxnro. While one can deter-inc whether e tail is flexed et en early ego cleeeifiootioe of the degree of floxure wee left until the enieele were of evening oco (three voeke) or longer if necoooery. in oertein ceeoe attire littore died free dysentery before they were of weaning ego. i‘heoo lit tore were re- corded for the proeenoo of e florere but not for the degree of flex. ore. ho dete were incorpcretod in thio theoie iron on: enieel that died before the prooenoo or ebeonce of e flomro we definitely deter- lined. it io etrongly indicated that there me e deoroeee in the incidence of auto-m1 in doorman; mu homeypoe notion of mo. flexed toiled otreie by the edninietretion of the perethyroid home to the pregaent female wider the conditioeo of thoeo experimento. :33 m o5 m Satefiohd 3:5 m onoéuzm 3:3 m unconfined deacon Banish coo defiance ammo. n 3.3 no.2 .3 one. a 09mm . 8.» a . Re. a an.» mama . S 33. a 8.3 8n. n moo. 9. Ram 9A m canon nonunion... unicorn «coo «on. ammo hum henna.“ omega» b gm; Hm." am." ”mm 38E Span TABLE VI PARATHYEOID AflD GCKTROL PCPULATICKS EEGREES OF FLBKDRE - EXPRESZED IE PEECBHTAGES Offsoring Degree of Floxuro 0 1 2 3 u °°n"°1 °n° 1~55 8.59 7.01 37.11 31.23 Parathyroid Control 2-80 2.80 11.21 30.8u 33.6u Parathyroid Combined 15.00 15.00 12.00 36.00 1u.oo (2 and 5) Parents Parathyroid 0.00 9.09 3.03 h8.h8 36.36 13.67 18.63 8.00 3.03 TABLE VII PARAEHYHOID humber of non-flexed individnnle found in Percent the parathyroid group Eon-flexed for everyone found in l. Parathyroid control 2. Control one Parathyro id Control Control Ono Parathyroid. 12.79? h.57 8.58 2 unite Parathyroid a 5 units 8.00; 2.86 5.37 Parathyroid J . (2 and 5 unite) 11.03; 3.9M 7.h0 combined TABLE VI II PARATHIROID Standard error of the "t“ diffornce Value Parathyroid Gon- 01.50 0.87 trol vs. Control One Parathyroid Oon— 03.88 2.57 trol vo. Paren- trqnoid 2 unite Parathyroid Con- 01$.ll 1.27 tnol vs. Para- thyroid 5 unite Parathyroid 2 05.26 0.91 units vs. Para- thyroid 5 unite Parathyroid 0on- 03.05 2.69 trolc vs. Pina- thyroid.2 end.5 unite Odde against the occurrence of a deviation oe greet no or greater then the deoimatod one. l.60:l 99.00:l 3.9011 1.7521 lhl.85:l PARATHYROID PERCENT NON- F LEXED I. CONTROL ONE PERCENT 2. PARATHYROID comaon. 3.PARATHYROID 2 UNITS 4. PARATHYROID s was '3" _. 5. PARATHYROID COMBINED (2 3‘5) l2y Ila .___. Id 9.. a, _ 7, 6. 5. 4. 3.» F.___ 2. IJL |W mfi nnnnnnnnnnn EACH GRADUATION EQUALS TEN'ANIMALS FIGURE IV PARATHYROID DEGREE OF FLEXURE IN THE OFFSPRING PARATHYROID CONTROL -— PARATHYROID COMBINED“--" (2 8 5 UNITS) 20A IO.- 2' 3 4 £3 DEGREE OF FLEXURE FIGURE V PARATHYROID DEGREE OF FLEXURE IN THE OFFSPRING CONTROLS —-- THYROXINE CONTROL PARATHYROID CONTROL —---- PARATHYROID UNITS w PERCENT THYROXINE W . ._ ALL DLUTIONS 40.. x 30. \‘ “x. \ 2O- \ l0» 0 I 2 3 4 ‘3 DEGREE OF FLEXURE FIGURE VI AVERAGE DEGREE OF FLEXURES — I. CONTROL ONE PARENTS 2. THYROXINE L3. PARATI-IYROI D 7‘4: CONTROL ONE 5.THYROXINE CONTROL OFFSPRING 6. PAR ATHYROID CONT ROL ZTHYROXINE ALL DILUTIQNIS _ 8.PARATI'IYROID 2/5 UNITS DEGREE OF FLEXURE 4. 3 .. ‘—I—1 2 .. FIGURE VII DEGREE OF FLEXURE OF THE PARENTS CON TRO L — THYROX 'NE ............. PARATHYROID “““ PERCENT so r w.. 0 i 2' 3 4 '5 e? DEGREE OF FLEXURE FIGURE VIII DEGREE OF FLEXURE OF PARATHYROID PARENTS AND OFFSPRING OF PARATHYROID 285 UNITS PARATHYROID PARENTS ----- PARATHYROID PERCENT 2&5 UNITS -—— 50‘ i E 3 4 5 '6 DEGREE OF FLEXURE FIGURE IX 25 niecneeion me dieeneeion concerning the relative importance of heredity and environment wee e loser conflict et one tine. In this expel-item. no in my othere deeling with heredity. the two tectore work together. the cannon concept of e. gene ie that the gene to en entity influencing e proceee of life refier then dioteting it. the environment: nodiflee the effecte of gene action. In thie experimt the only lenifeetetien of the flexed cue need no the lore obvious one. the toil neme. Annie. the belly-epot. end the lowered neteboliee were not inveetin- ‘ gated. the thyroid injectione into the premt tenelee of thie experi- eent hed no effect on the incidence of acme in the erupting. In- Jeeticne of the perethyroid honone into pregxent reaelee prodnoed n einii'ioent deereeee in the percentage of flexed ottepring. m ieveea- tigetion did not prove wet the parathyroid extreot noted directly eh the fetne. the effect ney here been indirect. through one eodificetien in the noteboliel of the pregnant nether. i‘he perethyroid her-nee eey reduce the degree of flewe or inhibit it “together. the totel inhibition of flexnre eee found in e limited. but etetieticelly eipificant. nn-her of enimle. In morel the average decree of neure eee lose ee e ooneequence or the injection. the re- duction effect of the degree of flemre wee meted by the 1’th that in the perethyroid grenpe the credee eero. one end two hed e higher repre— eentetion then in the oontrele. end the End» four end five were lower. the cherecter. flexed-toil. 1. exam: veriehle end there 1. only It elicht eipificent eorreleticn in the inheritance of the degree or flexnre. the larger ennhere of ottepring ere needed hetero eny oonolneion can he drew an to en redncing effect the parathyroid indentim any have had on the grade of nonre. 26 he met consider whether or not the hormone can pass through the placate from nether to fetus. One cannot assume such e peesege. That the thyroid hormone passes through the placenta free the foetel to the materm’ circulation wee gird: indirect support by the observations of Spielnen. Petersm and Fitch (19th) on the bovine. Vindle (19110) suggested en ap- parent led: of treneaieeion of the thyroid hormone in the bovine. In the human it scene probable that the thyroxine of the uther ie anil- able to the foetus. boomse it can traverse the placental terrier. The parathyroid hornene ie epperently unable to pass the placenta in degs (Vindle. 19%). In studies concerning the plaudits one must keep foremost in mind that the physiologic cheruteristice of the placente ere not content throughout chryonie end fetel deveIOpnent. nor ere they tb eels in ell species of enamels. This is sheen by the density end number of tissue layers eepereting netemel end foetal blood. The: type found in rodents consists only of n layer of endothelinn between the stern-l end foetal circulations. trith only e few cells between the foetal end Internal cir- culations it would seem that if e substance were to psee through the plo- cente. this type would be edventngeous. If the her-one con pess through Hog: the foetfi’tq‘f‘filscmtel circulation only after e certsin stage in the deveIOpnent of the placenta, it may have proved e barrier to the action of the hornone iron it my have been able to produce its greatest innnmce on the (one action in the dereloPing enhrye. i'he flexing ney hue begun Inch earlier than the fourteenth day and he dne to en eerlier lowered rate of netebolien. If this factor is the vital one. eerly inth forence with the process my be desirable. With the nethode used in this experiment early interferences with the developing foetus may not here been generelly ecoonplished with the 2? exception of the successful cesee where nonoflexed individuals were obtained by perethyreid indeetione. 0n perethyroid edninietrstion the phosphate level of the blood is reduced and celoinn is withdrm from the trnbecnlsr bone. the blood plasma value of calciun 1. high. the calcium level of the blood end the mechanism of the nervous system are intimately eseocieted. those changes may effect the foetus indirect- ly hr the chance in the netebolien of the nether or directly by ple- eutel trensniesion of e change in the composition of the uternel blood. —i'he perethyroid hora-one has n etetisticelly significant effect on the expression eéAf-lezed-teiled sue. the foot that the her-one did not prednce ell nornel tells leaves web to be investigated. but mggeste that the perethyroid could be an itportent factor in the ex- pression of the flexed-filled gene. Anderson. ll 5!. 1932 A preliminary study of hemopoieeie in young flexed talled.nice. Thesis for degree of M. 8.. Richigen State College. East Lansing. Michigan. Blank, 3. 1916-1917 Ifle Knickechwénze Ger Manse. .Arch. Ento. Mach. Org. Vol. he. pp. 333-h06. Best. 0. H. and H. B. Taylor 1939 The physiological basis of medical practice. 2nd edition, The Williams and Wilkins Company. Baltimore. Caeperi. e. and P. a. David who Journal of Heredity. Vol. 3 (10). pp. 1$227-$431. Chelsey. Paul 1935 Davelomneat of the short tailed Intent 1:: the house mouse. Journal of Experimental Zoology. Vol. 70(3). pp. h29oh53. Grew. P. A. E. and O. Auerbach 19h1 “Pigtail“ a hereditary tell abnor- mality in the house mouse. Hue musculus. Journal of Genetics. vol. 1.1 (2/3) pp. 267-27h. Clark. F. H. 193M The inheritance ani linkage relations of e new re- cessive epotting in the bones mouse. Genetioe. Vol. 19. pp. 365- 393- DeAberle. S. B. 1927 A study of hereditary'anemie in nice. American Journal of Anatomy. 701. no. pp. 219-2h9. Debrovolshale-Zevedekale. H. 19273 Eur 1a.mortification spontanee de le queue oboe 1e eourie noureannonee at our l'exietonce ales oar- ectere (faoteur) hereditaire "non viable." doe oomptee renius dee Seancee de la Societe de Biologie. vo1. 97. pp. llh-llG. DobrovolekeiapZevadekele, n. 1927» Bmdmrio. accompaenoo do conduree et "structure gentique' de la gueue obey la eonrie. Also. Une nonvelle mutation "bout flexible" de la gueue ohey le eonrie. Dos comtoo rcndus dos soancoe do In Sooiete ds Biologic. Vol. 97. pp. 1583-1537. DobrcvolekaiepZevadekaie. F.. 1925a L'irradiation doe testicules et l'hereditc chey 1e eourio. Archives de Biologie. Paris. Vol. 33’ PP. ”57'5010 . DobrovolekeiepZevedekaia. B. 1928b Houvells mutations dn type heli- coide de 13 quote chcy la couris. Doe comptos rendus doe Soonoee de la. Sooiete de Biologic. Vol. 98. pp. Boll-1306. Dobmvolekaie-Zavedokain. B. 19280 Sur une couche do sourie. precon- tant une mutabilite ineolite de la queue. Academic des Sciences. October. pp. 615-617. Dobrovolsknie-Zeveddkaia. H. 1928d Contribution e l‘etude de la struc- ture genetique dlun organe. Dee comptes rendue doe Seances do 1e Societe do Biologic. vol. 99. pp. llhO-llh}. DobrovolekeiePZevednkaie. H. 1929 The problem of species in View of the origin of some new forms in mice. Biological Reviews. Vol. 1“. pp- 327-351. DobrovolekeiapZewedekeie. H.. and Kobozioff. H. 1927o Sur la reproduc- tion dos courie uncures. Doe oomptec rendue dos Seances do la Societe de Biologie. Vol. 97. pp. 116.118. Dobrovolekeie-Zevedekoie. m. and Kobozioff. n. 1927b our one nouvollo mutation do 13 queue. 'queue filiforme.I obey le eouris. Des comptos rondue dos Seances do la Societe de Biologic. Vol. 97. pp. llhO»llh2. Dobrovolekeie—Zevedekeia. 3.. and Kobozioff. H. 1928 Suepension due developpement embryonneire d9une vertebre dans le queue do eouris et lee mutations qui en resultant. Dee ccmptcs renduc dos Seances do in Sooiete do Biologic. Vol. 98. pp. 1301-1303. mhrcvclckaiev-Zevedekeie. 11. end Koboziofi'. l}. 1930 “Gone-filament" et “pendeloquefi dour mtetione oppoeooe do 18 queue obey le eouris. Dee conptes rendus doe Seances do la Sooiete de Biologie. Vol. 101;. pp- 959-971- Duun. L. O. and 9. Gluedteohn-Schccnheimer 19142 Stub. e new mutation in the mouse. Journal of Heredity. Vol.1 33. p. 235. Dion. 1.. 0.. 8. Glueokeohn-Schoenhoimor and Vernon Bryson 19140 A new mutation in the mouse. Journal of IIorodity. Vol. 31. pp. 316.3148. GlueokeohnpSohoenheimor. S. 1938 The development of two teillece mu- tants in the house mouse. Genetics. Vol. 23 (6). pp. 573-581}. Gruneborg. E. 19142 The anemia of flexed nice (Mus nusoulus). l. . Static and dynamic haematology. Journal of Genetics. Vol. 1:3 1/2. pp. 1:5. 68. Eueetio. a. a. and Elizabeth Bette 1936 Flared—tailed Peronyccue. P. moniouletue. Journal of Heredity. Vol. 2‘]. pp. 73-75. Hunt. R. R. 1932 The flexed-tell mouse. Proceedings of the Sixth. International Congress of Genetics. Vol. 2. pp. 91-93. Hunt. H. 3.. a. Hixtor and D. Former 1933 Fiend tell in the nouee. £113 musculus. Genetics. Vol. 18. pp. 335. 365. Hunt. E. B..end D. Former 1928 Hosted tell. a mutation in the house mouse. Anatomical Records. Vol. 1&1. p. 117. Xenonoff. R. J. 1932 in emoryclogicel study of the pink (flexed) tailed muse. Proceedings of the Sixth International Gongreee of Genetics. 101. 2. p. 253. Kanonoi‘f. R. J. 1935 Effects of the flexed—tailed gas on the develop- ment of the house muse. Journal of tiorpholog. Vol. 58. pp. 117- 157. Kemenoff. B. J. 191% A cytolozical study of the embryonic livers (16- 13 days) of normal and flexed tail (anemic) nice. Genetics. Vol. 27. pp. 150. Loanee. T. and 3. O. facDowell 19h2 Screw tail. a.new mouse mutation. Genetics. Vol. 27. pp. 151-152. HacDowell. E. G. 192% .A method of determining the pronetel mortality in a. givm pregnancy of a mouse without affecting its eubeequent reproduction. Anatomical Records. Vol. 27. pp. 329-336. Mixter. Russell 1930 The blood of the flexed. tailed louse with some observations on the effects of inbreeding on the flexed tail strain. Thesis for degree of H. 8.. Michigan State college. East Lansing. Michigan. . Mixter. a. and a. 3. Hunt 1933 Anemia in the flexed «11.4 muse. Egg musculus. Genetics. Vol. 18. pp. 367-387. Plate. 1.. 1910 Die Knicksohwnnybleetoveriation. Vererbmgslehre and Deeyendenytheorie. Feetechr. 60. Geburtetoge Richard Hertvigs. 3d. 23537-610. Reed. 8. C. 1937 The inheritance and enzreeaion of fund. e new mutation in the houee mouse. Genetice..Vol. 22. pp. 1-13. Salvage. 1.. E. 1930 Tables of Pearson's Type III Function. Edward. Bro- there. Inc.. Ann Arbor. Michign. Spielman. A. A.. u. n. Peter-en and J. B. Fitch 19th The effect of thy. roidectomy on lactation in the bovine. Journal of Dairy Science. V01. 27. pp. ”hi—hh9. Windle. W. F. 19% Physiology of the Fetus. W. B. Saunders Company. Philadelphia.