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Meiotický efekt mutace genu MutS homolog 6 (Msh6) u dvou myších poddruhů / Meiotic effect of MutS homolog 6 (Msh6) mutation in two mouse subspecies

To study hybrid sterility our laboratory uses mouse strains PWD/Ph (PWD), derived from Mus musculus musculus wild mice and the common laboratory strain C57BL/6J (B6) mostly of Mus musculus domesticus origin as a model. Crossing between PWD female and B6 male results in sterile male progeny. F1 hybrid males carry defects in the repair mechanisms of asymmetric double-strand DNA breaks (DSBs). Functional interplay of SPO11 and PRDM9 proteins in the meiotic prophase I is necessary for repairs. Its defect leads to incorrect synapse formation between homologous chromosomes, leading to halt in spermatogenesis and thus male sterility. The formation of DSBs and their subsequent repair is essential for first meiotic division. The working hypothesis stems from the findings in yeast model, where supposed antirecombinatorial mechanism of mismatch repair genes Msh6 and Msh2 prevents DSBs repairs during meiosis. Despite the functional mechanism of these two genes is not explicitly known, existence of similar repair system in mice is presumed. Variety of methods was implemented in this thesis. The effects of Msh6 deletion on meiotic prophase I and sperm maturation were performed by designing guide RNAs for CRISPR/Cas9 for creation of three knock-outs in B6 mice. The PCR was used to amplify regions adjacent to the...

Identiferoai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:438317
Date January 2021
CreatorsFusek, Karel
ContributorsForejt, Jiří, Reifová, Radka
Source SetsCzech ETDs
LanguageCzech
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/masterThesis
Rightsinfo:eu-repo/semantics/restrictedAccess

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