Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11.
Spo11, a protein first identified in yeast, is thought to generate the chromosome breaks that initiate meiotic recombination. We now report that disruption of mouse Spo11 leads to severe gonadal abnormalities from defective meiosis. Spermatocytes suffer apoptotic death during early prophase; oocytes reach the diplotene/dictyate stage in nearly normal numbers, but most die soon after birth. Consistent with a conserved function in initiating meiotic recombination, Dmc1/Rad51 focus formation is abolished. Spo11(-/-) meiocytes also display homologous chromosome synapsis defects, similar to fungi but distinct from flies and nematodes. We propose that recombination initiation precedes and is required for normal synapsis in mammals. Our results also support the view that mammalian checkpoint responses to meiotic recombination and/or synapsis defects are sexually dimorphic.
Baudat
F
F
Cell Biology Program Memorial Sloan-Kettering Cancer Center New York, NY 10021, USA.
Manova
K
K
Yuen
J P
JP
Jasin
M
M
Keeney
S
S
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D023902:Chromosome Pairing; D002875:Chromosomes / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006066:Gonads / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016649:Primary Ovarian Insufficiency / Q000378:metabolism / Q000473:pathology; D011506:Proteins; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D012727:Sex Characteristics; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D000099257:Meiotic Recombination Protein SPO11
D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D011506:Proteins; D051135:Rad51 Recombinase; D000099257:Meiotic Recombination Protein SPO11; C495154:Rad51 protein, mouse