The t complex-encoded GTPase-activating protein Tagap1 acts as a transmission ratio distorter in mice

Nat Genet. 2005 Sep;37(9):969-73. doi: 10.1038/ng1617. Epub 2005 Aug 14.

Abstract

Transmission ratio distortion in the mouse is caused by several t-complex distorters (Tcds) acting in trans on the t-complex responder (Tcr). Tcds additively affect the flagellar movement of all spermatozoa derived from t/+ males; sperm carrying Tcr are rescued, resulting in an advantage for t sperm in fertilization. Here we show that Tagap1, a GTPase-activating protein, can act as a distorter. Tagap1 maps to the Tcd1 interval and has four t loci, which encode altered proteins including a C-terminally truncated form. Overexpression of wild-type Tagap1 in sperm cells phenocopied Tcd function, whereas a loss-of-function Tagap1 allele reduced the transmission rate of the t6 haplotype. The combined data strongly suggest that the t loci of Tagap1 produce Tcd1a. Our results unravel the molecular nature of a Tcd and demonstrate the importance of small G proteins in transmission ratio distortion in the mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomes, Mammalian*
  • Crosses, Genetic*
  • Female
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / physiology
  • Haplotypes*
  • Infectious Disease Transmission, Vertical*
  • Male
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / physiology*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / physiology*
  • Spermatozoa / physiology
  • Transgenes / physiology
  • t-Complex Genome Region

Substances

  • GTPase-Activating Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins