Molecular mechanisms of germ cell development

Molecular mechanisms of germ cell development

Ing. Zdeněk Trachtulec, Ph.D.

Ing. Zdeněk Trachtulec, Ph.D. — Project head

About us

The current fertility studies in model mammals move from the effects of single gene to genetic interactions important for human reproductive medicine that occur during spermatogenesis and oogenesis.

The Prdm9 gene (also called Meisetz) is necessary for both male and female meiosis and fertility in the laboratory mouse. The biochemical function of the PRDM9 protein is to methylate histones. The mouse, bovine, and human PRDM9 proteins specify the sites of meiotic recombination. However, PRDM9 is dispensable for fertility in the dog. PRDM9 polymorphisms were revealed in sterile human patients and PRDM9 variation contributes to instability of the human genome. We have identified Prdm9 as the first vertebrate hybrid sterility gene. Different Prdm9 mutations display different stages and degrees of spermatogenetic arrest on various backgrounds, indicating that the resulting phenotype is dependent on genetic interactions of Prdm9.

The aims of the project are: analyses of genes regulating germ cell development in mouse and rat testes and ovaries, interspecific differences important for translation studies; analyses of interactions and  incompatibilities of genes expressed in testes and ovaries; analyses of models of germ cell development defects that are affected by Prdm9, including complete meiotic arrest (azoospermia), limited fertility (reduced sperm count – oligospermia), sperm head malformations (teratozoospermia), and reproductive age defects (time-dependent arrest of germ cell development).

Videoabstract of a current paper (Flachs et al 2014, in Czech with optional English subtitles)

News

Events

Publications

2017

Mihola O, Trachtulec Z: A Mutation of the Prdm9 Mouse Hybrid Sterility Gene Carried by a Transgene. Folia Biol (Praha) 2017 63(1): 27-30.

2016

Balcova M, Faltusova B, Gergelits V, Bhattacharyya T, Mihola O, Trachtulec Z, Knopf C, Fotopulosova V, Chvatalova I, Gregorova S, Forejt J: Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse. PLoS Genet 2016 12(4): e1005906.

2015

Baker CL, Petkova P, Walker M, Flachs P, Mihola O, Trachtulec Z, Petkov PM, Paigen K: Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots. PLoS Genet 2015 11(9): e1005512.

2014

Flachs P, Bhattacharyya T, Mihola O, Piálek J, Forejt J, Trachtulec Z: Prdm9 incompatibility controls oligospermia and delayed fertility but no selfish transmission in mouse intersubspecific hybrids. PLoS One 2014 9(4): e95806.

2012

Flachs P, Mihola O, Simecek P, Gregorova S, Schimenti JC, Matsui Y, Baudat F, de Massy B, Pialek J, Forejt J, Trachtulec Z: Interallelic and Intergenic Incompatibilities of the Prdm9 (Hst1) Gene in Mouse Hybrid Sterility. PLoS Genetics 2012 8(11): e1003044.

Forejt J, Pialek J, Trachtulec Z: Hybrid male sterility genes in the mouse subspecific crosses. Evolution of the House Mouse. In: Macholan M, Ed. Macholan M, at all, Cambridge University Press 2012, 482-503.

2009

Mihola O, Trachtulec Z, Vlcek C, Schimenti JC, Forejt J: A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science 2009 323(5912): 373-5.

2008

Gregorová S, Divina P, Storchova R, Trachtulec Z, Fotopulosova V, Svenson KL, Donahue LR, Paigen B, Forejt J: Mouse consomic strains: exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies. Genome Res 2008 18(3): 509-15.

Trachtulec Z, Vlcek C, Mihola O, Gregorova S, Fotopulosova V, Forejt J: Fine haplotype structure of a chromosome 17 region in the laboratory and wild mouse. Genetics 2008 178(3): 1777-84.

2007

Mihola O, Forejt J, Trachtulec Z: Conserved alternative and antisense transcripts at the programmed cell death 2 locus. BMC Genomics 2007 8: 20.

2005

Trachtulec T, Mihola O, Vlček Č, Himmelbauer H, Pačes V, Forejt J: Positional cloning of the Hybrid sterility 1 gene: fine genetic mapping and evaluation of two candidate genes. Biological Journal of the Linnean Society 2005 84(3): 637-641.

Vyskocilova M, Trachtulec Z, Forejt J, Pialek J: Does geography matter in hybrid sterility in house mice? Biological Journal of the Lennean Society 2005 84(3): 663-674.