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

Transmission ratio distortion in the mouse is caused by several t- complex distorters ( Tcds) acting in trans on the t- complex responder ( Tcr)(1 - 4). 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 t(6) 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.