GENIC ACTION IN THE MOUSE 225 



under investigation, seems a critical feature in action of Miseries genes. Animals of 

 severely affected genotypes are anemic because of a metabolic defect, which either 

 specifically delays the synthesis of protoporphyrin or nonspecifically arrests erythroid 

 cell maturation at a stage when synthesis of protoporphyrin is an important metabolic 

 activity. 



TISSUE LOCALIZATION OF ACTION OF THE JF-GENE 



Genie action leading to the hematopoietic defect of Miseries anemic animals 

 definitely occurs in the hematopoietic cells themselves, rather than being imposed 

 from another part of the body. This has been demonstrated repeatedly by successful 

 implantation of hematopoietic cells from normal ww fetal liver into adult WW V and 

 juvenile WW V and lethally anemic WW mice. 84 ' no9 The implanted cells function 

 autonomously according to their own genotype, and the blood picture of the host 

 changes gradually but permanently to that of a normal mouse. It is interesting that 

 an initial very small inoculum of rapidly metabolizing cells eventually overwhelms a 

 large body of indigenous defective marrow. These experiments are also an interesting 

 demonstration that hematopoietic cells from the fetal liver at least can implant and 

 function in an adult manner in the marrow spaces of an adult. 



RADIATION RESPONSE OF NORMAL AND ANEMIC MICE 



The responses to irradiation of normal ww and anemic WW V animals are extremely 

 different. A dose of whole-body irradiation (200 r) which has very little effect upon 

 the blood picture of normal ww mice causes severe and prolonged reduction of the 

 hematocrit level, and, in some cases, death in littermate WW V anemic mice. 85 - 1109 

 The hematocrit level of surviving WW V mice returns to normal suddenly 3 to 4 weeks 

 after radiation treatment. Quantitative microscopic study of the marrow of normal 

 ww and anemic WW V mice at successive intervals after 200 r whole-body irradiation 

 revealed no difference between genotypes in initial destruction of marrow cells. 1098 

 The cellularity in both genotypes decreased sharply for the first two days after irradia- 

 tion. The marrow of ww individuals then regenerated rapidly and had returned 

 almost to pretreatment level by the fourth day after irradiation. That of WW V mice, 

 however, regenerated very slowly, and showed no visible increase in cellularity by the 

 eighth day after irradiation. Further evidence that radiation sensitivity depends in 

 this case upon the genotype of bloodforming tissue is found in studies of the reaction of 

 implanted WW V mice, with a normal blood picture, to increasing doses of X irradiation. 

 Their 30-day ld 50 dose corresponds closely to that of normal ww mice. 83 There is 

 even evidence that single doses of W or W v (in Ww and W v w animals) significantly 

 affect radioresistance. 83 



