To determine if TRIP13 deficiency prevents apoptosis triggered by asynapsis as in C. elegans, we analyzed mice that were doubly mutant for Spo11 and Trip13. SPO11 is a transesterase that is essential for the creation of genetically programmed DSB during leptonema of many organisms, including mice [18]. In C. elegans, spo-11 mutant gametes have extensive asynapsis, which triggers PCH-2 dependent apoptosis in pachynema [2]. In mice, Spo11 −/− spermatocytes are severely defective in homologous chromosome synapsis [34,35], and arrest with chromosomes in a state characteristic of the zygotene/pachytene transition (Figure 3H). Spermatocytes in Trip13Gt/Gt Spo11 −/− testes progressed maximally to that point before undergoing death (Figs 3I), well before the spindle checkpoint that eliminates achiasmate spermatocytes [36]. There was no evidence of metaphase I spermatocytes or postmeiotic spermatids in these testes, unlike those seen in Trip13 single mutants (Figure 3G). In contrast to the complete synapsis in Trip13Gt/Gt pachytene spermatocytes (Figure 5A), in which SPO11 is available in leptonema to initiate (via DSB induction, Figure S2A and S2B) a recombination-driven homolog search, chromosome synapsis in doubly mutant spermatocytes was highly disrupted as in Spo11 single mutants (Figure 5B and 5C). Identical studies were performed with mice deficient for Mei1, a vertebrate-specific gene also required for DSB formation and chromosome synapsis [37], with similar results (Figure 3J and 3K; immunocytology not shown).