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Analysis of dosage effect of speciation gene Prdm9 on fertility of mouse hybrids
Flachs, Petr ; Trachtulec, Zdeněk (advisor) ; Stopka, Pavel (referee) ; Král, Jiří (referee)
(eng) The phenomenon of hybrid sterility represents one of the evolutionary mechanisms that enables speciation. Only a few speciation genes have been uncovered. The only one found in mammals is Prdm9 (PR-domain 9). Data in the literature on the involvement of Prdm9 in decreased fertility of various semifertile hybrid males of house mouse subspecies were scarce before the results of this thesis were completed, despite that such males are much more frequent in nature than the fully sterile ones. Utilizing a panel of genetic tools and a battery of phenotyping tests, this thesis shows a central role of Prdm9 in fecundity of hybrids, including many fertility disorders and age dependency. Both increasing and reducing the Prdm9 gene dosage significantly elevated fertility parameters. Surprisingly, even the allele that in one copy causes full hybrid sterility increased F1 hybrid fertility when present in multiple copies. The PRDM9 protein also plays a role in identifying the sites of meiotic recombination. This study also points out the principles of allelic competition in determination of the sites of preferred recombination (hotspots), which suggests a possible link between both previously described Prdm9 roles. This thesis summarizes a set of three logically interconnected publications with the ambition...
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Establishment and phenotyping of three mouse congenic strains.
Flachs, Petr ; Trachtulec, Zdeněk (advisor) ; Vopálenský, Václav (referee)
Mouse congenic strains are widely used as an important genetic tool for various purposes of research. Congenic strains are special inbred strains in which part of the genome of one mouse is transferred to another by backcrossing the donor mouse to the recipient strain with appropriate selection. The classical ten-generation breeding protocol is commonly utilized and adapted for different experimental needs. Our department is focused on the study of hybrid sterility between two related mouse strains M. m. musculus and M. m. domesticus. The first aim of this work was the utilization of congenics to stabilize three transgenic lines, which previously helped to identify first mammalian hybrid sterility gene Hst1 as Prdm9 (Mihola et al, 2009). Bacterial artificial chromosomes (BACs) present in transgenes encompassed several genes including Prdm9. The second goal was to look for some new phenotypes of our congenic strains, which may be causally associated with genes encoded by the BACs, as well as an additional research on the hybrid sterility phenomena. We established three new congenic strains on C57BL/6J (B6) background and found significant differences between transgenics versus their littermate controls in weights of testis, gonadal fat, body, liver, and heart. Powered by TCPDF (www.tcpdf.org)
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