232 PHYSIOLOGIC GENETICS 



of his races of rabbits, including various pigment types. Genetic susceptibility to 

 seizures in the house mouse has been found in a number of pigment types, including 

 black animals. 1343 Inhibition has not been studied very much. However, in the 

 epidermal cells of the skin of the guinea pig there is an easily demonstrable sulf hydril 

 inhibitor which does not correlate quantitatively with differences in pigmentation, but 

 which does definitely inhibit the formation of pigment. 433 This has also been verified 

 by Dr. Rothman in human skin. 1078 I do not know whether it has ever been found 

 for the mouse. It may relate to Dr. Coleman's point on inhibition. I do not think 

 this has ever been studied in relation to genes except in the guinea pig. 



Dr. Coleman: I did not mean to imply that susceptibility to audiogenic seizures 

 and defects in pigmentation are always related. There are many other possibilities 

 here. There is one mutant I have worked on at the Jackson Laboratory which 

 does not have the dilute gene, that is, it has the normal intense pigmentation (DD) 

 but has a lowered phenylalanine-hydroxylase activity which is about the same level as 

 that found in the DBA. This animal also goes into seizures of an identical pattern to 

 the DBA, suggesting again that the phenylalanine hydroxylase level is important in the 

 induction or seizures in these animals. Although no pigment defect is observed, this 

 also suggests that more than one gene is involved in the control of phenylalanine 

 hydroxylase. 



Dr. Ginsburg : I did not disagree with the observations on phenylalanine hydroxy- 

 lase activity, which are extremely interesting and need additional investigation. 

 There did seem to be an impression that this activity was correlated with the pigmenta- 

 tion, and I wish to point out that seizures occur in mice and rabbits of various 

 pigment types and that inhibitory mechanisms of relevance to the problem of pigment 

 formation are known but neglected. 



Dr. Herzenberg : Has anyone in this audience any information on the following 

 question? It has been suggested that more genes of physiologic importance may be 

 found in the mouse by applying sensitivity of various inbred strains to drugs or loading 

 them with sugars and seeing what the excretion levels of these sugars might be. Has 

 anyone any information about whether this has been done ? 



Dr. Russell: Water is a fairly good drug, and there certainly are fine examples of 

 fairly simple, genetic differences in reactions to water which have been found recently. 

 There are a number of kinds of polydipsic mice ; 267 the imbibition of alcohol varies 

 between strains. 820 



The only thing I would like to say in closing is to express the hope that I have been 

 able to give, through these examples, an idea of how one may go about studying the 

 action in particular genes in mice, why it is a complicated process, and how I believe 

 that differentiation is, in a sense, a tool as well as a problem. 



