Spata22, a novel vertebrate-specific gene, is required for meiotic progress in mouse germ cells.
The N-ethyl-N-nitrosourea-induced repro42 mutation, identified by a forward genetics strategy, causes both male and female infertility, with no other apparent phenotypes. Positional cloning led to the discovery of a nonsense mutation in Spata22, a hitherto uncharacterized gene conserved among bony vertebrates. Expression of both transcript and protein is restricted predominantly to germ cells of both sexes. Germ cells of repro42 mutant mice express Spata22 transcript, but not SPATA22 protein. Gametogenesis is profoundly affected by the mutation, and germ cells in repro42 mutant mice do not progress beyond early meiotic prophase, with subsequent germ cell loss in both males and females. The Spata22 gene is essential for one or more key events of early meiotic prophase, as homologous chromosomes of mutant germ cells do not achieve normal synapsis or repair meiotic DNA double-strand breaks. The repro42 mutation thus identifies a novel mammalian germ cell-specific gene required for meiotic progression.
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Sophie
S
La Salle
Kristina
K
Palmer
Marilyn
M
O'Brien
John C
JC
Schimenti
John
J
Eppig
Mary Ann
MA
Handel
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D018389:Codon, Nonsense / Q000235:genetics; D005260:Female; D007247:Infertility, Female / Q000235:genetics / Q000503:physiopathology; D007248:Infertility, Male / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D011506:Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D013090:Spermatocytes / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D011506:Proteins; C573338:SPATA22 protein, mouse