The t-complex-encoded guanine nucleotide exchange factor Fgd2 reveals that two opposing signaling pathways promote transmission ratio distortion in the mouse

  1. Hermann Bauer1,
  2. Nathalie Véron1,
  3. Jürgen Willert1, and
  4. Bernhard G. Herrmann1,2,3
  1. 1 Max-Planck-Institute for Molecular Genetics, Department of Developmental Genetics, Berlin 14195, Germany;
  2. 2 Charité-University Medicine Berlin, Institute of Medical Genetics, CBF, Berlin 12200, Germany

Abstract

Transmission ratio distortion (TRD), the preferential inheritance of the t haplotype from t/+ males, is caused by the cooperative effect of four t-complex distorters (Tcd1–4) and the single t-complex responder (Tcr) on sperm motility. Here we show that Fgd2, encoding a Rho guanine nucleotide exchange factor, maps to the Tcd2 region. The t allele of Fgd2 is overexpressed in testis compared with wild type. A loss-of-function allele of Fgd2 generated by gene targeting reduces the transmission ratio of the t haplotype th49, directly demonstrating the role of Fgd2 as Distorter. Fgd2 identifies a second Rho G protein signaling pathway promoting TRD.

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  1. doi: 10.1101/gad.414807 Genes & Dev. 2007. 21: 143-147 Copyright © 2007, Cold Spring Harbor Laboratory Press

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