A protein kinase encoded by the t complex responder gene causes non-mendelian inheritance

Males heterozygous for the t-haplotype form of mouse chromosome 17 preferen tially transmit the t-chromosome to their progeny. Several distorter/steril ity loci carried on the t-haplotype together impair flagellar function in a ll spermatozoa whereas the responder, Tcr, rescues t-sperm but not wild-typ e sperm. Thus, t-sperm have an advantage over wild-type sperm in fertilizin g egg cells. We have isolated Tcr by positional cloning and show that it is a member of a novel protein kinase gene family, designated Smok, which is expressed late during spermiogenesis, Smok kinases are components of a sign al cascade which may control sperm motility, Tcr has a reduced kinase activ ity, which may allow it to counterbalance a signalling impairment caused by the distorter/sterility loci, Tcr transgene constructs cause non-mendelian transmission of chromosomes on which they are carried, which leads to sex- ratio distortion when Tcr cosegregates with the Y chromosome.