Mutations in Serac1 or Synj2 cause proximal t haplotype-mediated male mouse sterility but not transmission ratio distortion

doi:10.1073/pnas.0407970102

Mutations in Serac1 or Synj2 cause proximal t haplotype-mediated male mouse sterility but not transmission ratio distortion

^*The Jackson Laboratory, Bar Harbor, ME 04609; and ^‡Program in Biological Chemistry, Bates College, Lewiston, ME 04240

Edited by Mary F. Lyon, Medical Research Council, Harwell, Didcot, United Kingdom (received for review October 26, 2004)

Abstract

Transmission ratio distortion (TRD) and sterility are male-specific quantitative trait phenomena associated with the mouse t haplotype. TRD occurs in t haplotype-heterozygous males and is caused by the deleterious action of distorter products on sperm bearing a wild-type responder locus. It has been proposed that t-mediated male sterility is a severe manifestation of TRD caused by homozygosity for distorter loci; thus, the distorter and sterility loci would be identical. In this, study a transgenic approach was used to identify the proximal sterility locus, tcs1 (S1), and test its role in TRD. Mice transgenic for a wild-type bacterial artificial chromosome (BAC) derived from the S1-critical region were bred onto t haplotype backgrounds. Mating results conclusively showed that the BAC is sufficient to restore fertility in otherwise sterile males. Multiple mutations were identified in the t alleles of Synj2 and Serac1, two genes in the BAC; thus, they are candidates for S1. In addition, whereas the BAC transgene rescued sterility, it had no effect on TRD. These results uncouple the proximal t haplotype sterility locus, S1, from TRD, demonstrating that S1 and the proximal distorter locus, D1, are not the same gene.

Footnotes

↵ ¶ To whom correspondence should be addressed. E-mail: aplancha{at}mdibl.org.
↵ † Present address: Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853.
↵ § Present address: Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672.
Author contributions: J.C.S. and A.P. designed research; J.C.S., J.L.R., and A.P. performed research; J.C.S., J.L.R., and A.P. analyzed data; and A.P. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: TRD, transmission ratio distortion; BAC, bacterial artificial chromosome; Tg, transgenic; OFM, offspring per female per month; SERAC1, serine active site containing 1; IP₃, inositol-3,4,5-trisphosphate; ADAM2, β-fertilin; INPP5, inositol polyphosphate 5-phosphatase.