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RESEARCH COMMUNICATION

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

¹ Max-Planck-Institute for Molecular Genetics, Department of Developmental Genetics, Berlin 14195, Germany; ² Charité-University Medicine Berlin, Institute of Medical Genetics, CBF, Berlin 12200, Germany

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 t^h49, directly demonstrating the role of Fgd2 as Distorter. Fgd2 identifies a second Rho G protein signaling pathway promoting TRD.

[Keywords: Mouse; transmission ratio distortion; testis; sperm motility; Rho; G proteins]

Received October 17, 2006; revised version accepted November 24, 2006.

E-MAIL herrmann{at}molgen.mpg.de; FAX 49-30-8413-1229.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.414807

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