Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy

dc.contributor.author Singh, Ravindra
dc.contributor.author Howell, Matthew
dc.contributor.author Singh, Natalia
dc.contributor.author Seo, Joonbae
dc.contributor.author Ottesen, Eric
dc.contributor.author Singh, Ravindra
dc.contributor.department Biomedical Sciences
dc.contributor.department Veterinary Pathology
dc.date 2018-02-17T13:54:12.000
dc.date.accessioned 2020-06-30T00:53:45Z
dc.date.available 2020-06-30T00:53:45Z
dc.date.copyright Fri Jan 01 00:00:00 UTC 2016
dc.date.issued 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="http://dx.doi.org/10.1038/srep20193" target="_blank">10.1038/srep20193</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/bms_pubs/9/
dc.identifier.articleid 1008
dc.identifier.contextkey 8207481
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath bms_pubs/9
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/11216
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/bms_pubs/9/2016_Singh_SevereImpairment.pdf|||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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