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Spermatogenesis associated 22 is required for DNA repair and synapsis of homologous chromosomes in mouse germ cells
Author(s) -
Hays E.,
Majchrzak N.,
Daniel V.,
Ferguson Z.,
Brown S.,
Hathorne K.,
La Salle S.
Publication year - 2017
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12315
Subject(s) - synapsis , biology , meiosis , synaptonemal complex , spermatogenesis , homologous chromosome , homologous recombination , prophase , gametogenesis , germ cell , genetics , null allele , mutant , microbiology and biotechnology , gene , endocrinology , embryogenesis
Summary Analysis of the N ‐ethyl‐ N ‐nitrosourea ( ENU )‐induced repro42 mutation previously identified spermatogenesis associated 22 ( Spata22 ) as a gene required for meiotic progression and fertility in both male and female mice, but its specific contribution to the process was unclear. Here, we report on a novel, null allele of Spata22 ( Spata22 Gt ) and confirm its requirement for germ cell development. Similar to repro42 mutant mice, histological and mating analyses indicate that gametogenesis is profoundly affected in Spata22 Gt/Gt males and females, resulting in infertility. Cytological examination confirms that germ cells do not progress beyond zygonema and meiotic arrest is linked to impairment of both synapsis and DNA repair. Analysis of SPATA 22 distribution reveals that it localizes to foci associated with meiotic chromosomes during prophase I and that the number of foci peaks at zygonema; there are also more SPATA 22 foci in oocytes than in spermatocytes. Furthermore, SPATA 22 co‐localizes with a number of proteins involved in meiotic recombination, including RAD 51, DMC 1, and MLH 1, and is present until mid‐pachynema, suggesting a role in resolution of recombination intermediates. In fact, SPATA 22 co‐localizes with MLH 1 in more than 20% of foci at pachynema. Analysis of Spata22 Gt/Gt meiocytes confirms that SPATA 22 is required for localization of MEIOB but not RPA (two proteins known to interact with SPATA 22), and immunoblotting corroborates that production of MEIOB is indeed decreased in the absence of SPATA 22. Together, these data suggest that SPATA 22 is required for both meiotic recombination and synapsis during meiosis in mice.