GENIC ACTION IN THE MOUSE 223 



attempting to bring together the differing effects of this multiple allelic series, Bennett, 

 Badenhausen, and Dunn 76 suggest there are "some grounds for suggesting that at least 

 four different lethal /-alleles affect pathways which lead to progressively higher types 

 of neural differentiation. The mutation T . . . appears to affect a different pathway 

 in differentiation, that leading through the chorda-mesoderm. It is not easy to 

 reconcile this diversity in physiological effects with 'unity of action' of a locus that 

 appears on genetical grounds to be a unit not resolved by recombination." In the 

 face of this confusion, it is comforting to remember that tracing the widely differing 

 paths affected by T and t alleles has nevertheless been very helpful in explaining their 

 complementation in the viability of 77 hybrids. 



Some genes with shape-determining effects in embryonic life act through mech- 

 anisms other than induction. An interesting example is short ear, in which a primary 

 effect appears to be reducing growth of cartilage. Since cartilaginous growth is most 

 conspicuous in fetal life, many effects of short ear are apparent at this time. However, 

 recent experiments with healing of broken ribs have shown that a metabolic deficiency 

 in cartilage growth persists into adult life in short-eared mice. 486 



MURINE HEREDITARY ANEMIAS 



Analysis of genie action in the causation of six different types of inherited anemias 

 in mice is a major concern in current physiologic genetic investigations at the Jackson 

 Laboratory. Genes at three of the loci, Dominant spotting (W, W' t W v ), 503 - 50i - 1091 ' 

 1102. 1106 g tee i ^ s[d^ 83. 1155 an( j Hertwig's anemia (anan) 7 * 1 cause varying degrees of 

 macrocytic anemia. Homozygous flexed-anemia (ff) animals suffer from a transitory 

 macrocytic siderocytic anemia limited to fetal and neonatal life. 505 ' 506 ' 885 Animals 

 homozygous for either jaundice {jaja) 1280 or hemolytic anemia (haha) 83 suffer from severe 

 hemolytic disease with abnormal nucleated erythrocytes and extensive postnatal 

 jaundice. Animals of five of the available genotypes die shortly after birth, and several 

 other genotypes are semilethal. Each anemia seems to present a different defect in 

 hematopoiesis, and each is present before birth. We are very hopeful that some of 

 these anemia-producing genes may provide especially favorable material for identifying 

 the metabolic error in a tissue primarily affected and possibly may even give clues as 

 to factors limiting genie action to these tissues. The murine anemias named above 

 which we are studying do not exhaust the list of available types. Another dominant- 

 spotting allele has been reported (W a ). 907 A very interesting independently in- 

 herited anemia, diminutive (dm) , with associated skeletal defects, has also been described 

 recently. 1279 



It is essential, of course, to have an accurate description of the erythron and the 

 hematopoietic tissue in each mutant genotype. It is also important to measure ac- 

 curately quantitative differences between the effects of different alleles within the same 

 series and between genes of different series, avoiding difficulties from variations in the 

 genetic backgrounds on which these genes are segregating. As with various entities 



