Mouse molecular genetics

Mouse molecular genetics

Prof. MUDr. Jiří Forejt, DrSc.

Prof. MUDr. Jiří Forejt, DrSc. — Project head

The Institute of Molecular Genetics of the Czech Academy of Sciences

About us

While the analysis in human genomics is currently focusing on the genome-wide association studies (GWAS), the mouse model offers a complementary approach using genetic fractionation of polymorphisms on the model of the chromosome substitution strains (= consomic strains) and the recombinant inbred (RI) strains (see the current international project, Collaborative Cross). So far only 4 complete panels of the chromosome substitution strains exist in the world. Two of them were prepared in the USA, one in our laboratory and one in Japan.

We were the first to use a powerful genetic polymorphism that occurred during evolution of two mouse sub-species; Mus m. musculus and Mus m. domesticus to create a panel of consomic strains. Mice from our consomic strains have been partly phenotyped in the PHENOME program in The Jackson Laboratory, Bar Harbor, Maine, USA.

These mice serve as a universal tool for studying wide range of complex human diseases as mentioned above. The consomic strains will find a special use in studying the modifier genes and for studying the genes controlling production of functional sperm.

Analysis of a mouse model of male infertility of interspecies hybrids. The model gains information of the role of individual genes in infertility by following the cellular, subcellular and molecular traits associated with male infertility in mouse sub-species Mus m. musculus and Mus m. domesticus hybrids. The new knowledģe obtained from the mouse infertility model will be applied on data from human male infertility studies. As an example, our recent discovery of Prdm9 gene as mouse hybrid sterility prompted subsequent follow up studies of this gene in patients of human infertility clinics.

More info HERE

News

Publications

2019

Papanikos F, Clément JAJ, Testa E, Ravindranathan R, Grey C, Dereli I, Bondarieva A, Valerio-Cabrera S, Stanzione M, Schleiffer A, Jansa P, Lustyk D, Fei JF, Adams IR, Forejt J, Barchi M, de Massy B, Toth A,: ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice. Mol Cell. Jun 6;74(5):1069-1085.e11, 2019

Lustyk D, Kinský S, Ullrich KK, Yancoskie M, Kašíková L, Gergelits V, Sedlacek R, Chan YF, Odenthal-Hesse L, Forejt J, Jansa P.: Genomic structure of Hstx2 modifier of Prdm9-dependent hybrid male sterility in mice. Genetics 213 (3), 1047-1063 Nov 2019. DOI: /10.1534/genetics.119.302554.

2018

Gregorova, S., Gergelits, V. Chvatalova, I., Bhattacharyya, T., Valiskova B., Fotopulosova V., Jansa, P., Wiatrowska, D., Forejt, J.,: Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice. Elife Mar 14;7. pii: e34282, 2018.

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 Apr 22;12(4):e1005906. doi: 10.1371/journal.pgen.1005906.

Forejt J. Genetics: Asymmetric breaks in DNA cause sterility. Nature. 2016 Feb 11;530(7589):167-8. doi: 10.1038/nature16870.

2015

Kropáčková L, Piálek J, Gergelits V, Forejt J, Reifová R. Maternal-foetal genomic conflict and speciation: no evidence for hybrid placental dysplasia in crosses between two house mouse subspecies. J Evol Biol. 2015 Mar;28(3):688-98. doi: 10.1111/jeb.12602. Epub 2015 Mar 6.

2014

Jansa P, Homolka D, Blatny R, Mistrik M, Bartek J, Forejt J. Dosage compensation of an aneuploid genome in mouse spermatogenic cells. Biol Reprod. 2014 Jun;90(6):124. doi: 10.1095/biolreprod.114.118497.

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 Apr 22;9(4):e95806. doi: 10.1371/journal.pone.0095806.

Bhattacharyya T, Reifova R, Gregorova S, Simecek P, Gergelits V, Mistrik M, Martincova I, Pialek J, Forejt J. X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids. PLoS Genet. 2014 Feb 6;10(2):e1004088. doi: 10.1371/journal.pgen. 1004088.

2013

Schughart K, Libert C; SYSGENET consortium (including Forejt J), Kas MJ: Controlling complexity: the clinical relevance of mouse complex genetics. Eur J Hum Genet. 2013 Nov;21(11):1191-6. doi: 10.1038/ejhg.2013.79. Epub 2013 May 1. Review.

Bhattacharyya T, Gregorova S, Mihola O, Anger M, Sebestova J, Denny P, Simecek P, Forejt J: Mechanistic basis of infertility of mouse intersubsoecific hybrids. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E468-77. doi: 10.1073/pnas.1219126110. Epub 2013 Jan 17.

2012

Dzur-Gejdošová, M., Šimeček, P., Gregorová, S., Forejt, J.: Genetic architecture of hybrid sterility in the house mouse. Evolution 2012; DOI: 10.1111/j.1558-5646.2012.01684.x

Forejt, J.: Hybrid sterility, mouse. In: Encyclopedia of Genetics, 2e 2012; S. Brenner and J. Miller, Eds. Academic Press, London, New York, in press.

2009

Mihola, O., Trachtulec, Z., Vlček, C., Schimenti, J.C., Forejt, J: A mouse speciation gene encodes a meiotic Histone H3 methyltransferase. Science 2009; 323:373—375.

2008

Gregorová, S., Divina, P., Storchová, R., Trachtulec, Z., Fotopulosová, V., Svenson, K.L., Donahue, L.R., Paigen, B., Forejt, J.: Mouse consomic strains: Exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies. Genome Research 2008; 18:509-515.

Team

Prof. MUDr. Jiří Forejt, DrSc. Prof. MUDr. Jiří Forejt, DrSc.

Prof. MUDr.
Jiří Forejt, DrSc.

Head of Group Genetically defined mice models as a tool for studying human diseases

jiri.forejt@img.cas.cz
+420325873258

Teaching

Offered topics

thesis author thesis name thesis type