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Sex chromosome missegregation is particularly common and can lead to sterility or to aneuploid offspring (e.g. individuals with Turner or Klinefelter syndrome). Despite major implications for health and reproduction, modifiers of meiotic SAC robustness and the subsequent apoptotic response in male mammals remain obscure. Levels of SAC proteins, e.g. MAD2, are critical for normal checkpoint function in many experimental systems, but surprisingly, apparently not in male meiosis, as indicated by the lack of chromosome segregation defects reported earlier in Mad2+\/- spermatocytes. To directly test whether MAD2 levels impact the meiotic response to missegregating chromosomes, we utilized Spo11\u03b2-onlymb mice that are prone to non-exchange X-Y chromosomes. We show that reduced MAD2 levels attenuate the apoptotic response to missegregating sex chromosomes and allow the formation of aneuploid sperm. These findings demonstrate that SAC protein levels are critical for the efficient elimination of aberrant spermatocytes.<\/jats:p>","DOI":"10.1242\/dev.149492","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T00:10:23Z","timestamp":1494893423000},"source":"Crossref","is-referenced-by-count":9,"title":["Reduced MAD2 levels dampen apoptotic response to non-exchange sex chromosomes and lead to sperm aneuploidy"],"prefix":"10.1242","author":[{"given":"Imrul","family":"Faisal","sequence":"first","affiliation":[{"name":"Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, FI-00290 Helsinki, Finland"},{"name":"Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, FI-00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-8997","authenticated-orcid":false,"given":"Liisa","family":"Kauppi","sequence":"additional","affiliation":[{"name":"Genome-Scale Biology Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, FI-00290 Helsinki, Finland"},{"name":"Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, FI-00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2021042608523911500_DEV149492C1","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1073\/pnas.91.2.524","article-title":"Detection of nondisjunction and recombination in meiotic and postmeiotic cells from XYSxr [XY,Tp(Y)1Ct] mice using multicolor fluorescence in situ hybridization","volume":"91","author":"Ashley","year":"1994","journal-title":"Proc. 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