226 PHYSIOLOGIC GENETICS 



RESPONSE OF NORMAL AND ANEMIC MICE TO ERYTHROPOIETIC STIMULI 



Studies of the responses of ww normal and WW V anemic mice to known erythro- 

 poietic stimuli have yielded valuable information both on the pattern of M^-gene action 

 and on the nature of hemostatic mechanisms. Twelve moderate-sized daily doses of a 

 purified erythropoietin 807 which has induced extra erythropoiesis in normal animals of 

 six different species, 696 were administered to normal ww and anemic WW animals. 

 In all cases the normal ww mice responded to the treatment with greatly increased 

 hematocrit level, marked reticulocytosis, and increased total blood volume. 1104 The 

 WW V mice, however, were completely unaffected by the injections. This genotypic 

 difference in reaction to a known erythropoietic stimulus depends upon the genetic 

 nature of the bloodforming tissue. The response to erythropoietin of WW V mice 

 implanted with ww cells is exactly comparable to that of ww mice. 697 



There is at least one erythropoietic stimulus to which ww and WW V mice respond 

 equally. If normal and If-anemic mice are subjected to reduced atmospheric pres- 

 sure 503 or to lowered oxygen tension at normal pressure, 697 animals of both genotypes 

 respond with reticulocytosis and increased hematocrit level. The difference in 

 response of WW mice to different stimuli demonstrates clearly that there must be 

 more than one fundamental erythropoietic stimulus and suggests that the basic genie 

 action in Miseries anemias may be related to the phase of erythropoiesis affected by 

 treatment with Borsook-type extracted erythropoietin. It is very tempting to speculate 

 that the maturation arrest of WW V mice, their special radiation sensitivity through 

 delayed marrow regeneration, and their inability to respond to erythropoietin may all 

 be different aspects of the same basic phenomenon. 



ANALYSIS OF JF-SERIES AND STEEL PLEIOTROPISMS 



In addition to suffering from the macrocytic anemia already described, animals 

 of all double-dominant TT-genotypes {WW, WW V , W'W V , etc.) lack pigment in the 

 hair and are almost completely sterile. The sterility results from failure of the pri- 

 mordial germ cells to multiply during their migration to the gonadal ridge, between 

 the eighth and twelfth days of embryonic life. 879 - 880 In this analysis the primordial 

 germ cells were visualized in sectioned whole embryos by alkaline-phosphatase staining. 

 The association of reduced germ-cell number with the double-dominant genotypes was 

 determined on a statistical basis rather than by genotypic identification of individual 

 embryos. Only matings between two heterozygous parents produced embryos with 

 defective germ-cell numbers at 9, 10, 11, and 12 days, and the proportion of defective 

 embryos at each age was close to 25 per cent. The germ-cell defect seems to be com- 

 pletely determined by the twelfth day of embryonic life, since 12-16 day fetal gonads 

 transferred to a neutral site with a rich blood supply developed autonomously according 

 to their genotype. 1107 In this study using older fetuses as gonad donors, individual 

 genotypic identification was possible. All double-dominant fetuses were pale at 12-16 

 days due to their hematopoietic defect. Luxate, a third-chromosome gene approxi- 



