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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)1,2,3,4. 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 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.

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Figure 1: Tagap1 is a candidate for Tcd1.
Figure 2: Expression analysis and GAP activity assays of Tagap1.
Figure 3: Construction of gain- and loss-of-function alleles of Tagap1.
Figure 4: Model of the role of Tcds and Tcr in TRD.

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We thank M.F. Lyon for mice carrying the t haplotypes used in this study, D. Solter for long-term support, K. Wertz for the knockout allele of Tagaps in ES cells, B. Ledermann for BALB/c ES cells, D. Walther for Rho cDNA clones, M. Mallo for advice on ES-cell culture, B. Kanzler for pronuclear and ES-cell injections and L. Hartmann and the animal facilities of the Max Planck Institutes of Immunobiology and of Molecular Genetics for animal work. This project was supported by a grant from the Deutsche Forschungsgemeinschaft to B.G.H.

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Correspondence to Bernhard G Herrmann.

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Supplementary Table 1

Oligonucleotide primer sequences and PCR conditions used. (PDF 52 kb)

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Bauer, H., Willert, J., Koschorz, B. et al. The t complex–encoded GTPase-activating protein Tagap1 acts as a transmission ratio distorter in mice. Nat Genet 37, 969–973 (2005).

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