Immunogenetic Studies of the Mouse and the Rat

This thesis includes immunogenetic investigations of three systems in mice and rats. The first part deals with theta (Thy-1) antigens in mice. Results and conclusions are presented from three separate experiments: 1) Crosses were made between inbred mice, and electrophoretic analysis of serum transferrin and kidney malic enzyme, along with serological detection of Thy-1, aligned the three loci in the following order on chromosome 9: Trf --- Mod-1 --- Thy-1. This work led to a revision of the previously-accepted map of chromosome 9 in the mouse. 2) Sublines of inbred AKR mice, which differ in susceptibility to leukemias, were found to differ from one another by two of these same chromosome 9 genetic markers (Mod-1 and Thy-1). 3) Two alleles of Thy-1 were found to be segregating in one wild mouse colony (from the Southern California area) which has an unusually high incidence of lymphomas. Only one allelic product was detected in another wild mouse colony, which is lymphoma-resistant. However, the inheritance of either allele of Thy-1 could not be associated with an individual predisposition to lymphoma. The second part of the thesis deals with rat lymphoid cell antigens. In rats, the major histocompatibility complex is called H-1. A study of the membrane-associated glycoprotein products of this genetic region was conducted, employing a number of biochemical techniques, including electrophoretic separation on one- dimensional and two-dimensional gels, and microsequence analysis. The study showed that the major transplantation antigens in rats are closely similar to one another, and homologous to those of other species. The results demonstrate that there may be two transplantation antigens encoded by each of three H-1 haplotypes. The alloantigens associated with the H-1 linked immune response region in rats (Ia antigens) were also studied, and evidence is presented for the existence of two separate Ia antigens in each rat haplotype studied. An immunogenetic analysis of the levels of a mouse carcino-embryonic antigen known as alpha fetoprotein (AFP) is contained in the last part of this thesis. An extremely sensitive radioimmunoassay was developed to detect levels of AFP in inbred strains and genetic crosses of mice which produce high or low adult concentrations of this fetal protein. The results from this study indicate no genetic association between the structural gene for albumin and the factor(s) regulating the level of serum AFP. There is also evidence that the high AFP level seen in some of the backcross progeny of the particular cross investigated is not determined by a single recessive gene.