Molecular structure of Tcp-10 genes from the t complex responder locus.

Male transmission ratio distortion (TRD) is a property of mouse t haplotypes which requires the t complex responder locus (Tcr). Tcr has been localized to a 70-160 kb region in t haplotypes. A candidate gene for the responder, called Tcp-10bt, has been cloned and is one member of a highly related gene family called Tcp-10 (formerly T66). Molecular evidence suggests that unique alternative splicing of the Tcp-10bt gene may be responsible for the mutant responder activity. Here we present the intron/exon structure of a representative Tcp-10 gene, and the characterization of alternative polyadenylation sites. The Tcp-10 genes contain 12 exons which span approximately 21 kb of DNA. At least six different polyadenylation sites are used, and none have a perfect consensus signal. This appears to be a common feature associated with testes-expressed transcripts. Since the gene we have analyzed is absent from many t haplotypes without apparent consequence, and no corresponding cDNAs have been isolated, it was speculated to be a pseudogene. However, no major sequence differences were found within the coding sequence to conclude that Tcp-10pst is a pseudogene.