The Nucleoside Diphosphate Kinase Gene Nme3 Acts as Quantitative Trait Locus Promoting Non-Mendelian Inheritance

• DOI: 10.1371/journal.pgen.1002567
• Publication Date: 2012-03-15T21:50:25Z
• Authors: Hermann Bauer; Sabrina Schindler; Yves Charron; Jürgen Willert; Barica Kusecek; Bernhard G. Herrmann
• Keywords: Male; rho GTP-Binding Proteins; 0301 basic medicine; Heredity; Molecular Sequence Data; Quantitative Trait Loci; Mice, Transgenic; QH426-470; NM23 Nucleoside Diphosphate Kinases; Spermatozoa; Mice; 03 medical and health sciences; Phenotype; Mutation; Genetics; Sperm Motility; Animals; Amino Acid Sequence; Protein Kinases; Research Article; t-Complex Genome Region

The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (> 95%) from heterozygous (t/+) males to their offspring. This phenotype termed transmission ratio distortion (TRD) caused by interaction responder (Tcr) with several quantitative trait loci (QTL), distorters (Tcd1 Tcd4), all located within t-haplotype region. Current data suggest that collectively impair motility sperm derived t/+ males; t-sperm rescued responder, whereas (+)-sperm remains partially dysfunctional. Recently we have identified two regulators RHO small G proteins. Here show nucleoside diphosphate kinase gene Nme3 QTL TRD. Reduction dosage targeting wild-type allele enhanced rate phenocopied distorter function. Genetic biochemical analysis showed t-allele harbors mutation (P89S) compromises enzymatic activity protein genetically hypomorph. Transgenic overexpression reduced transmission, proving it be distorter. We propose NME3 interacts signaling cascades through hyperactivation SMOK, responder. deleterious effect counter-balanced SMOK(Tcr), dominant-negative exclusively expressed in t-sperm, thus permitting behaviour preferential t-haplotype. In addition, previously reported association NME family members somatic cell metastasis, conjunction our involving motility, suggests functional conservation between mechanisms for control cells spermatozoa.