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Genomická architektura a molekulární mechanismy hybridní sterility myši. / Genomic architecture and molecular mechanisms of hybrid sterility in mice.

Hybrid sterility is one of the reproductive isolation mechanisms restricting gene flow between the related species and leading to speciation. PR domain containing 9 (Prdm9), the only known vertebrate hybrid sterility gene, determines the sites of programmed DNA double-strand breaks (DSBs) and thus specifies hotspots of meiotic recombination but in hybrids between two mouse subspecies causes failure of meiotic chromosome synapsis and hybrid male sterility. In the present study on sterile hybrids, the five smallest autosomes were more prone to asynapsis. To manipulate with the synapsis rate, random stretches of consubspecific homology were inserted into several autosomal pairs. Twenty seven or more megabases of consubspecific sequence fully restore synapsis in a given autosome. Further, at least two symetric DN double-strand breaks per chromosome were necessary for successful synapsis. Moreover, F1 hybrids had sperm when synapsis was rescued in at least three of four segregating chromosomes. To verify the assumption of a lack of symmetric DSBs in meiotic chromosomes of sterile males the chemotherapeutic drug cisplatin was used to induce exogenous DNA DSBs. Cells treated with 5 mg/kg and 10 mg/kg of cisplatin showed increased number of DSBs monitored by immunostaining of RPA and DMC1 sites and...

Identiferoai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:438168
Date January 2021
CreatorsVališková, Barbora
ContributorsForejt, Jiří, Janko, Karel, Macholán, Miloš
Source SetsCzech ETDs
LanguageCzech
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/doctoralThesis
Rightsinfo:eu-repo/semantics/restrictedAccess

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