title: Spermatogenesis associated 22 is required for DNA repair and synapsis of homologous chromosomes in mouse germ cells.
abstract: 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 (Spata22Gt) and confirm its requirement for germ cell development. Similar to repro42 mutant mice, histological and mating analyses indicate that gametogenesis is profoundly affected in Spata22Gt/Gtmales 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 SPATA22 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 SPATA22 foci in oocytes than in spermatocytes. Furthermore, SPATA22 co-localizes with a number of proteins involved in meiotic recombination, including RAD51, DMC1, and MLH1, and is present until mid-pachynema, suggesting a role in resolution of recombination intermediates. In fact, SPATA22 co-localizes with MLH1 in more than 20% of foci at pachynema. Analysis of Spata22Gt/Gtmeiocytes confirms that SPATA22 is required for localization of MEIOB but not RPA (two proteins known to interact with SPATA22), and immunoblotting corroborates that production of MEIOB is indeed decreased in the absence of SPATA22. Together, these data suggest that SPATA22 is required for both meiotic recombination and synapsis during meiosis in mice.
authors.affiliation: Department of Biochemistry, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hays
authors.affiliation: Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Majchrzak
authors.affiliation: Department of Biochemistry, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA.
authors.forename: V
authors.initials: V
authors.lastname: Daniel
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences, Midwestern University, Downers Grove, IL, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Ferguson
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences, Midwestern University, Downers Grove, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences, Midwestern University, Downers Grove, IL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hathorne
authors.affiliation: Department of Biochemistry, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: La Salle
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D023902:Chromosome Pairing / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism*; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C573338:SPATA22 protein, mouse
keywords: 
  Spata22
  ; infertility; meiosis; mouse; oogenesis; prophase I; recombination; spermatogenesis; synapsis