Academic Journal
The Role of the Msh2 Mismatch Repair Gene in the Prdm9-Driven Hybrid Male Sterility in the House Mouse.
| Title: | The Role of the Msh2 Mismatch Repair Gene in the Prdm9-Driven Hybrid Male Sterility in the House Mouse. |
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| Authors: | Fusek K; Department of Cell Biology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic.; Laboratory of Mouse Molecular Genetics, Institute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic.; Laboratory of Epigenetic Regulations, Institute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic., Jansa P; Laboratory of Mouse Molecular Genetics, Institute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic.; Laboratory of Epigenetic Regulations, Institute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic., Forejt J; Laboratory of Mouse Molecular Genetics, Institute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic.; Laboratory of Epigenetic Regulations, Institute of Molecular Genetics, Czech Academy of Sciences, 142 20 Prague, Czech Republic. |
| Source: | Genes [Genes (Basel)] 2026 Jul 12; Vol. 17 (7). Date of Electronic Publication: 2026 Jul 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel : MDPI |
| MeSH Terms: | MutS Homolog 2 Protein*/genetics , MutS Homolog 2 Protein*/metabolism , Infertility, Male*/genetics , Infertility, Male*/pathology , Histone-Lysine N-Methyltransferase*/genetics , Histone-Lysine N-Methyltransferase*/metabolism , DNA Mismatch Repair*/genetics, Spermatogenesis/genetics ; Spermatozoa/metabolism ; Animals ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout |
| Abstract: | Background/objectives: Hybrid sterility arises when two fully fertile populations produce sterile offspring, representing a key postzygotic barrier to gene flow between emerging species. In the sterile hybrid males of Mus musculus domesticus (M. m. domesticus, represented by the C57BL/6J strain, hereafter B6) and Mus musculus musculus (M. m. musculus, represented by the wild-derived PWD/Ph strain), meiotic prophase I exhibits extensive autosomal asynapsis, pachytene arrest, and an absence of mature spermatozoa. This sterility results from Prdm9 allelic incompatibility, which is modulated by the X-linked Hstx2 locus, recently identified as the Mir465 microRNA. While this two-locus incompatibility is the major cause of sterility, additional modifiers may further contribute to the phenotype. In particular, the DNA mismatch repair protein MSH2 recognizes DNA sequence heterology and enforces anti-recombination in yeast. This raises the possibility that Msh2 could amplify the effects of subspecific sequence divergence in mouse hybrids. Methods: To test this hypothesis, we generated an Msh2 knockout on a B6 genetic background and assessed its effect on the hybrid sterility phenotype in F1 hybrid and backcross males. Results: Loss of MSH2 did not restore fertility in F1 hybrids. Testes weight remained low, and no mature spermatozoa were detected. In contrast, a modest partial rescue was observed in backcross males carrying the critical Prdm9/Mir465 genotype, with improvements in testes weight and sperm count. Conclusions: We examined the role of the Msh2 gene in arresting spermatogenesis in intersubspecific mouse hybrids. The results show that sterility is predominantly governed by the Prdm9-Mir465 incompatibility, and that DNA mismatch repair has a minor, genetic background-dependent effect. |
| Grant Information: | 275023 Charles University; 22-29928S Czech Science Foundation |
| Contributed Indexing: | Keywords: Dobzhansky–Muller incompatibility; Mir465; Msh2; Mus musculus; Prdm9; anti-recombination; hybrid male sterility; meiosis; mismatch repair; pachytene arrest |
| Substance Nomenclature: | EC 3.6.1.3 (MutS Homolog 2 Protein) EC 2.1.1.43 (prdm9 protein, mouse) EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) EC 3.6.1.3 (Msh2 protein, mouse) |
| Entry Date(s): | Date Created: 20260728 Date Completed: 20260729 Latest Revision: 20260730 |
| Update Code: | 20260730 |
| PubMed Central ID: | PMC13409646 |
| DOI: | 10.3390/genes17070795 |
| PMID: | 42510835 |
| Database: | MEDLINE |
| ISSN: | 2073-4425 |
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| DOI: | 10.3390/genes17070795 |