The proposed research has two specific aims. The first is to define the physiological effects of t mutations which result in the distorted (non-Mendelian) transmission of the mutations from male mice. These studies - determining cAMP content, adenylate cyclase and cAMP phosphodiesterase activities and cAMP-dependent protein phosphorylation patterns - will be done on spermatozoa which carry complete t mutations and on those which carry either proximal partial or distal partial deletions of the T/t complex. Completion of these comparative studies will enable us to confirm our hypothesis that the abnormal transmissions are caused by aberrant levels of cAMP which, in turn, result in abnormal patterns of protein phosphorylation. Use of the partially deleted t mutant chromosomes should enable us to map the factors controlling these physiological parameters. The second specific aim is a test of our hypothesis that the phenotypic syndromes associated with the T/t complex are controlled by the unique H-2 haplotypes which are linked to the t mutations. In this series of studies we will inject plasmids carrying wild-type H-2 sequences into t/t zygotes and determine the effect of the inserted H-2 DNA on embryo lethality and male transmission frequency.
