The Dobzhansky-Muller model of incompatibilities explains reproductive isolation between species by incorrect epistatic interactions. Although the mechanisms of speciation are of great interest, no incompatibility has been characterized at the gene level in mammals. The Hybrid sterility 1 gene (Hst1) participates in the arrest of meiosis in F(1) males of certain strains from two Mus musculus subspecies, e.g., PWD from M. m. musculus and C57BL/6J (henceforth B6) from M. m. domesticus. Hst1 has been identified as a meiotic PR-domain gene (Prdm9) encoding histone 3 methyltransferase in the male offspring of PWD females and B6 males, (PWD×B6)F(1). To characterize the incompatibilities underlying hybrid sterility, we phenotyped reproductive and meiotic markers in males with altered copy numbers of Prdm9. A partial rescue of fertility was observed upon removal of the B6 allele of Prdm9 from the azoospermic (PWD×B6)F(1) hybrids, whereas removing one of the two Prdm9 copies in PWD or B6 background had no effect on male reproduction. Incompatibility(ies) not involving Prdm9(B6) also acts in the (PWD×B6)F(1) hybrids, since the correction of hybrid sterility by Prdm9(B6) deletion was not complete. Additions and subtractions of Prdm9 copies, as well as allelic replacements, improved meiotic progression and fecundity also in the progeny-producing reciprocal (B6×PWD)F(1) males. Moreover, an increased dosage of Prdm9 and reciprocal cross enhanced fertility of other sperm-carrying male hybrids, (PWD×B6-C3H.Prdm9)F(1), harboring another Prdm9 allele of M. m. domesticus origin. The levels of Prdm9 mRNA isoforms were similar in the prepubertal testes of all types of F(1) hybrids of PWD with B6 and B6-C3H.Prdm9 despite their different prospective fertility, but decreased to 53% after removal of Prdm9(B6). Therefore, the Prdm9(B6) allele probably takes part in posttranscriptional dominant-negative hybrid interaction(s) absent in the parental strains.

• MeSH
• alely MeSH
• chiméra * genetika   fyziologie   MeSH
• fertilita genetika   MeSH
• genetická epistáze * MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• hybridizace genetická MeSH
• mapování chromozomů MeSH
• meióza MeSH
• mužská infertilita genetika   MeSH
• myši MeSH
• reprodukční izolace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• prdm9 protein, mouse MeSH Prohlížeč

Hybrid sterility is a common postzygotic reproductive isolation mechanism that appears in the early stages of speciation of various organisms. Mus musculus musculus and Mus musculus domesticus represent two recently separated mouse subspecies particularly suitable for genetic studies of hybrid sterility. Here we show that the introgression of Chr X of M. m. musculus origin (PWD/Ph inbred strain, henceforth PWD) into the genetic background of the C57BL/6J (henceforth B6) inbred strain (predominantly of M. m. domesticus origin) causes male sterility. The X-linked hybrid sterility is associated with reduced testes weight, lower sperm count, and morphological abnormalities of sperm heads. The analysis of recombinant Chr Xs in sterile and fertile males as well as quantitative trait locus (QTL) analysis of several fertility parameters revealed an oligogenic nature of the X-linked hybrid sterility. The Hstx1 locus responsible for male sterility was mapped near DXMit119 in the central part of Chr X. To ensure full sterility, the PWD allele of Hstx1 has to be supported with the PWD allelic form of loci in at least one proximal and/or one distal region of Chr X. Mapping and cloning of Hstx1 and other genes responsible for sterility of B6-X PWD Y B6 males could help to elucidate the special role of Chr X in hybrid sterility and consequently in speciation.

• MeSH
• akrozomální reakce MeSH
• alely MeSH
• chromozom X * MeSH
• fenotyp MeSH
• genetická vazba * MeSH
• genetické markery MeSH
• genotyp MeSH
• křížení genetické MeSH
• lokus kvantitativního znaku MeSH
• monoklonální protilátky chemie   MeSH
• mužská infertilita genetika   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• rekombinantní proteiny chemie   MeSH
• sexuální faktory MeSH
• spermie patologie   MeSH
• testis patologie   MeSH
• ženská infertilita genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• genetické markery MeSH
• monoklonální protilátky MeSH
• rekombinantní proteiny MeSH

We have generated a high-resolution genetic map, 0.071 cM per backcross animal, of the 13 cM T-H2 region of the mouse Chromosome (Chr) 17. The map contains two phenotypic loci, T and Hst1, 12 RFLP markers, and 24 microsatellite loci. The Hst1 gene was mapped to a chromosomal interval contained within a single 580-kb YAC clone. The FFEH11 YAC is 0.44 cM long and carries, besides the Hst1 gene, five polymorphic DNA markers and recombination breakpoints of six backcross animals. Two candidate genes for Hst1 were identified based on their location and testicular expression. These are Tbp and D17Ph4e. The submilliMorgan map of the T-H2 region revealed significant clustering of (CA)n loci. The clustering, if shown to be a common feature in the mouse genome, may cause gaps in the physical map of the mouse genome.

• MeSH
• DNA primery MeSH
• genetické markery MeSH
• genotyp MeSH
• H-2 antigeny genetika   MeSH
• hybridizace genetická MeSH
• mapování chromozomů * MeSH
• molekulární sekvence - údaje MeSH
• multigenová rodina MeSH
• mužská infertilita genetika   MeSH
• myši inbrední C3H MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• polymorfismus konformace jednovláknové DNA MeSH
• rekombinace genetická MeSH
• sekvence nukleotidů MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• DNA primery MeSH
• genetické markery MeSH
• H-2 antigeny MeSH