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While SMN is one of the most scrutinized proteins associated with neurodegeneration, its gender-specific role in vertebrates remains unknown. We utilized a mild SMA model (C\/C model) to examine the impact of low SMN on growth and development of mammalian sex organs. We show impaired testis development, degenerated seminiferous tubules, reduced sperm count and low fertility in C\/C males, but no overt sex organ phenotype in C\/C females. Underscoring an increased requirement for SMN expression, wild type testis showed extremely high levels of SMN protein compared to other tissues. Our results revealed severe perturbations in pathways critical to C\/C male reproductive organ development and function, including steroid biosynthesis, apoptosis and spermatogenesis. Consistent with enhanced apoptosis in seminiferous tubules of C\/C testes, we recorded a drastic increase in cells with DNA fragmentation. SMN was expressed at high levels in adult C\/C testis due to an adult-specific splicing switch, but could not compensate for low levels during early testicular development. Our findings uncover novel hallmarks of SMA disease progression and link <jats:italic>SMN<\/jats:italic> to general male infertility.<\/jats:p>","DOI":"10.1038\/srep20193","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T10:49:36Z","timestamp":1454410176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy"],"prefix":"10.1038","volume":"6","author":[{"given":"Eric W.","family":"Ottesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia N.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonbae","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Whitley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra N.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,2]]},"reference":[{"key":"BFsrep20193_CR1","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1007\/s13311-014-0293-y","volume":"11","author":"T Awano","year":"2014","unstructured":"Awano, T., Kim, J. 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