Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy Singh, Ravindra Howell, Matthew Singh, Natalia Seo, Joonbae Ottesen, Eric Singh, Ravindra
dc.contributor.department Biomedical Sciences
dc.contributor.department Veterinary Pathology 2018-02-17T13:54:12.000 2020-06-30T00:53:45Z 2020-06-30T00:53:45Z Fri Jan 01 00:00:00 UTC 2016 2016-01-01
dc.description.abstract <p>Spinal muscular atrophy (SMA) is caused by low levels of survival motor neuron (SMN), a multifunctional protein essential for higher eukaryotes. 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 <em>SMN</em> to general male infertility.</p>
dc.description.comments <p>This article is from <em>Scientific Reports</em> 6 (2016): 20193, doi:<a href="" target="_blank">10.1038/srep20193</a>. Posted with permission.</p>
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dc.identifier archive/
dc.identifier.articleid 1008
dc.identifier.contextkey 8207481
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath bms_pubs/9
dc.language.iso en
dc.source.bitstream archive/|||Sat Jan 15 02:22:55 UTC 2022
dc.source.uri 10.1038/srep20193
dc.subject.disciplines Other Animal Sciences
dc.subject.disciplines Veterinary Anatomy
dc.subject.disciplines Veterinary Pathology and Pathobiology
dc.subject.disciplines Veterinary Physiology
dc.title Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy
dc.type article
dc.type.genre article
dspace.entity.type Publication
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