Targeted mutagenesis of a candidate t complex responder gene in mouse t haplotypes does not eliminate transmission ratio distortion.
Transmission ratio distortion (TRI) associated with mouse t haplotypes causes +/t males to transmit the t-bearing chromosome to nearly all their offspring. Of the several genes involved in this phenomenon, the t complex responder (Tcrt) locus is absolutely essential for TRD to occur. A candidate Tcrt gene called Tcp10bt was previously cloned from the genetically defined Tcrt region. Its location, restricted expression in testis, and a unique postmeiotic alternative splicing pattern supported the idea that Tcp10bt was Tcrt. To test this hypothesis in a functional assay, ES cells were derived from a viable partial t haplotype, and the Tcp10bt gene was mutated by homologous recombination. Mutant mice were mated to appropriate partial t haplotypes to determine whether the targeted chromosome exhibited transmission ratios characteristic of the responder. The results demonstrated that the targeted chromosome retained full responder activity. Hence, Tcp10bt does not appear to be Tcrt. These and other observations necessitate a reevaluation of genetic mapping data and the actual nature of the responder.
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
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Ewulonu
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Schimenti
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Kuemerle
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Magnuson
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Schimenti
D000818:Animals; D002460:Cell Line; D005260:Female; D006239:Haplotypes; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases