GENETIC CONTROL OF SERUM TRANSFERRIN TYPE IN MICE.

Relationships between genes and proteins are being defined in detail through genetic studies of the fine structure of the chromosome and chemical analyses of the molecular structures of genetically variant proteins. The most extensive chromosomal fine structure investigation has been done with bacteriophage.1 The best evidence concerning the effects of mutation on protein structure has come from chemical and genetic studies of human hemoglobins.2 Eventually genetic fine structure studies and protein structure analyses will be combined for given genetic loci and the proteins they control. The most elegant studies of this type will probably be done with microorganisms, because of their advantages for genetic study. It is important, however, also to extend our understanding of gene-protein relationships in higher animals, particularly mammals. The hemoglobin work has demonstrated that such investigations are possible in mammals. It should be worthwhile to analyze other protein variant systems in the same way, in order better to understand the detailed mechanisms and relationships inivolved in the genetic control of a variety of different proteins. Such studies require variant systems which can be readily isolated and purified, which have been shown to be genetically determined, and which, preferably, occur in species adapted to intensive genetic study. A genetic difference has been observed in the 3-lactoglobulins of cow's milk,3 and a number of physicochemical studies of these differing proteins have been carried out.4-6 Genetically determined antigenic differences in the 7-globulins of rabbits have been studied by gel diffusion and immunoelectrophoresis.7-9 Chemical investigations of rabbit y-globulins have been in progress for many years. Investigations of fractions obtained by papain digestion by Porter"? and by peptic digestion by Nisonoff et al.ll offer hope for identification of the antigenic differences with specific portions of the molecule. Observations with starch gel electrophoresis of a number of genetically determined serum protein variant systems in humans (reviewed by Smithies12), cattle,l3 14 sheep,14 goats,14 horses,"5 and swine"6 have provided materials which may prove useful for structural studies. Adequate techniques are available so that many of these serum proteins could be isolated and purified without serious difficulty. However, with all of the species in which serum protein variants have been identified, as well as with the human hemoglobin studies, there is difficulty in conducting intensive genetic studies of the sort which would be desirable for the most precise definitions of gene-protein relationships in mammals, in terms of allelism, linkage, intragenic recombination, etc. The most favorable mammalian species available for such investigations is the mouse. Well-defined linkage groups, adequate markers, the availability of highly inbred lines, and a short generation interval make it very useful for genetic study. Hemoglobin variants have been observed in the mouse and have been well studied genetically."7 However, no other well-defined protein variants have been reported in the mouse. Thompson et al.l8 have described an apparent genetic difference