Mouse model for the study of SPO11 splicing isoform during mouse meiosis

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NIDDK	CELLBIO-17

Authors

• F Pratto
• M Bellani
• R Camerini-Otero

Abstract

Meiotic recombination is initiated by the formation of programmed DNA double-strand breaks (DSB) catalyzed by the SPO11 protein. It is a widely conserved protein and two major isoforms (α and β) are readily detected in testes. In males, these two forms have distinct expression kinetics. SPO11β transcripts are found early in prophaseI whereas SPO11α transcripts (exon2 skipped) are mainly synthesized late in meiosis. Since breaks are introduced in early prophase, the simplest model suggests that the larger form of SPO11 is the catalytic form that generates the DSBs, while the smaller form has an alternative role in late prophase. To address whether the two isoforms have distinct functions we have generated a SPO11α specific transgenic mouse by deleting exon 2 in a BAC containing the Spo11 locus. We found that, although timely expressed, SPO11α fails to make breaks and meiosis progression is arrested. Our findings favor the notion of SPO11β as the only isoform responsible of introducing the breaks. As for the alternative role for SPO11α we introduced DSB exogenously in a SPO11-/-SPO11α+/- mouse. These breaks result in some synapsis, which is more appreciable in the presence of SPO11α arguing for a role in either promoting or stabilizing homologous synapsis.

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