GENIC ACTION IN THE MOUSE 219 



may determine enzymatic structure comes from recent studies 213 of tyrosinase 

 activity in mice carrying a new allele of the albino series, Himalayan (c h ), discovered 

 recently in the Jackson Laboratory. 487 This mutant almost certainly contains a 

 qualitatively different tyrosinase from those found in mice with any of the other alleles 

 of the albino series. If one gene in an allelic series is responsible for a qualitative 

 enzymatic difference, it is probable that the entire series acts by determining enzymatic 

 structure. 



Gene-induced difference in enzymatic activity is not always, of course, attributable 

 to change in enzymatic structure. Recent studies of the mutant allele dilute (d) and 

 dilute-lethal (d l ) have demonstrated a deficiency of the enzyme, phenylalanine hydro- 

 xylase, associated with genie substitutions at this locus. 214 Further studies have 

 indicated, however, that the genie action involved is an inhibition of activity of an 

 enzyme formed quite independently of the genes at the dilute locus. 



FUNCTION OF GENES AND TISSUES 



A relatively large proportion of the analyzed effects of substitutions of single genes 

 in the mouse has been traced to differences in the structural differentiation of 

 certain specific tissues only. For these genotypes, the majority of tissues of an affected 

 animal, except in terminal stages of a lethal condition, cannot be distinguished from 

 those of an unaffected littermate. The choreic movements and deafness associated 

 with six different independent mutant genotypes in the mouse have been traced to 

 dedifferentiation of Corti's organ, degeneration of the spiral ganglion, and abnormali- 

 ties in the stria vascularis. 248, 249, 4 " Since effects of these mutants compensate each 

 other, in crosses, it is clear that there are at least six different ways in which tissues of 

 the murine vestibular apparatus can fail. The locomotor difficulties, whole-body 

 tremor, muscular spasms, and early mortality found in wobbler-lethal mice (wlwl) all 

 appear to result from degeneration of the myelin sheath surrounding nerve processes. 273 

 The retina of a mouse with retinal degeneration (rdrd) develops normally for the first ten 

 days after birth, then begins to show degeneration of the rods, while those of normal 

 littermates continue differentiation. 1258, 1313 



For each of the mutant types so far described in this section, histologic difference 

 from normal has been described which involves an inability of affected tissue to com- 

 plete normal differentiation or to maintain normal structure. It is probable that each 

 defect is due either to a metabolic error specific to the abnormal tissue or one imposed 

 upon this tissue by a correlative influence from some other part of the body, that is, 

 either local or distant site of original genie action. For many tissues it is difficult to 

 obtain critical evidence as to this cellular localization, although the limitation of 

 visible difference to one tissue suggests greater probability of local genie action. A 

 somewhat equivocal suggestion as to the site of genie action in retinal degeneration 

 may be derived from an experiment involving organ culture in vitro of genotypically 

 normal and rdrd eyes explanted at the stage (10 days) when degeneration is first 



