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 | |
relation.isAuthorOfPublication | d5765265-0e5d-4de9-8e17-19842ab75544 | |
relation.isAuthorOfPublication | 30dd0ac9-28a2-4363-bac0-4f19aa596e2f | |
relation.isOrgUnitOfPublication | 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9 | |
relation.isOrgUnitOfPublication | cf38d7e3-b5f8-4859-83e3-ae8fab6a4c5f |
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