218 PHYSIOLOGIC GENETICS 



and the answers obtained contribute to understanding in these fields. At present 

 the house mouse is the most widely studied mammalian species other than man, because 

 of the large number and variety of named genes and the availability of many inbred 

 strains with genetic homogeneity and well-established physiologic characteristics. 

 The purpose of this paper is discussion of the special problems encountered in studies 

 of the physiologic genetics of the mouse. f 



The fact of differentiation leads to complications never encountered in micro- 

 organisms. Tracing the pathway between site of original action of the gene and 

 observed character is frequently a major problem. When the site and time of original 

 genie action have been established, it is often difficult to devise methods of analyzing 

 metabolic processes within the affected cells. Examples of profitable approaches 

 surmounting these obstacles have been selected from recent literature and current 

 research projects. It is hoped that presentation of these pertinent examples, and 

 discussion of their relationship to fundamental genetic questions, will lead to some 

 basic generalizations regarding the methodology of mammalian physiologic genetics. 



GENES, PROTEINS, AND ENZYMATIC ACTIVITY 



It is probable that the primary activity of most, if not all, genes is determination of 

 the specificity of an intracellular macromolecule. Very few of the inherited charac- 

 teristics recognized in mammals represent these immediate genie products. In the 

 few cases, however, where this may be true, that is, where the observed effect of a genie 

 substitution is change in the structure of a protein molecule, the fact of cellular dif- 

 ferentiation may simplify analysis of genie action. The production of this protein may 

 be limited to particular types of cells and may represent a very large part of the total 

 metabolic activity of these cells, greatly facilitating biochemical and physical chemical 

 analysis. Determination of the globin structure of hemoglobin appears to fall in this 

 class, 102 ' 104, 1181 and experimental genetic analysis of hemoglobin pattern in the 

 mouse, described in this volume by Dr. Popp, shows great promise. Little insight has 

 yet been gained into the developmental processes channeling the metabolism of 

 hematopoietic cells into this limited range of activity, a problem which presents a 

 challenge for future investigations. 



The action of the well-known albino series of genes, affecting intensity of hair 

 pigmentation in the mouse and other mammalian species, may very well be determina- 

 tion of the structure of a tyrosinase molecule. Genie substitutions at this locus definitely 

 alter tyrosinase activity, 382 which could mean either alterations in concentration of 

 identical enzymes or qualitative alteration of the enzyme molecule similar to that 

 seen in certain tyrosinase mutants 598 in Neurospora. Evidence that this series of genes 



t The research reported in this paper, which originates from the Physiological Genetics 

 Group at the Roscoe B. Jackson Memorial Laboratory, has been supported by a contract 

 between the U.S. Atomic Energy Commission and by grants to the laboratory from the 

 U.S. Public Health Service and the American Cancer Society. 



