shani mutation in mouse affects splicing of Spata22 and leads to impaired meiotic recombination Journal Article


Authors: Petrillo, C.; Barroca, V.; Ribeiro, J.; Lailler, N.; Livera, G.; Keeney, S.; Martini, E.; Jain, D.
Article Title: shani mutation in mouse affects splicing of Spata22 and leads to impaired meiotic recombination
Abstract: Recombination is crucial for chromosome pairing and segregation during meiosis. SPATA22, along with its direct binding partner and functional collaborator, MEIOB, is essential for the proper repair of double-strand breaks (DSBs) during meiotic recombination. Here, we describe a novel point-mutated allele (shani) of mouse Spata22 that we isolated in a forward genetic screen. shani mutant mice phenocopy Spata22-null and Meiob-null mice: mutant cells appear to form DSBs and initiate meiotic recombination, but are unable to complete DSB repair, leading to meiotic prophase arrest, apoptosis and sterility. shani mutants show precocious loss of DMC1 foci and improper accumulation of BLM-positive recombination foci, reinforcing the requirement of SPATA22-MEIOB for the proper progression of meiotic recombination events. The shani mutation lies within a Spata22 coding exon and molecular characterization shows that it leads to incorrect splicing of the Spata22 mRNA, ultimately resulting in no detectable SPATA22 protein. We propose that the shani mutation alters an exonic splicing enhancer element (ESE) within the Spata22 transcript. The affected DNA nucleotide is conserved in most tetrapods examined, suggesting that the splicing regulation we describe here may be a conserved feature of Spata22 regulation. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Keywords: gene mutation; exon; missense mutation; nonhuman; animal cell; mouse; spermatocyte; meiosis; allele; animal tissue; gene; apoptosis; molecular dynamics; messenger rna; chromosome pairing; genetic conservation; rna splicing; cell mutant; chromosome segregation; nucleotide; prophase; enhancer region; splicing; meiotic recombination; gametogenesis; double strand break repair; male; article; meiob; shani gene; spata22 gene
Journal Title: Chromosoma
Volume: 129
Issue: 2
ISSN: 0009-5915
Publisher: Springer  
Date Published: 2020-06-01
Start Page: 161
End Page: 179
Language: English
DOI: 10.1007/s00412-020-00735-8
PUBMED: 32388826
PROVIDER: scopus
PMCID: PMC7546082
DOI/URL:
Notes: Article -- Export Date: 1 July 2020 -- Source: Scopus
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MSK Authors
  1. Scott N Keeney
    120 Keeney
  2. Nathalie Josette Lailler
    10 Lailler
  3. Devanshi Jain
    5 Jain