Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11

Spo11, a protein first identified in yeast, is thought to generate the chro mosome breaks that initiate meiotic recombination. We now report that disru ption of mouse Spoil leads to severe gonadal abnormalities from defective m eiosis. 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 meioti c recombination, Dmc1/Rad51 focus formation is abolished. Spo11 (-/-) meioc ytes also display homologous chromosome synapsis defects, similar to fungi but distinct from flies and nematodes. We propose that recombination initia tion precedes and is required for normal synapsis in mammals. Our results a lso support the view that mammalian checkpoint responses to meiotic recombi nation and/or synapsis defects are sexually dimorphic.