The t-complex-encoded guanine nucleotide exchange factor Fgd2 reveals that two opposing signaling pathways promote transmission ratio distortion in the mouse.
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.
Bauer
Hermann
H
Max-Planck-Institute for Molecular Genetics, Department of Developmental Genetics, Berlin 14195, Germany. herrmann@molgen.mpg.de
Véron
Nathalie
N
Willert
Jürgen
J
Herrmann
Bernhard G
BG
D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D018390:Gene Targeting; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D056427:t-Complex Genome Region
C485666:Fgd2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins