TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy

Abstract Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C +/+) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monito...

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Autores principales:	Matthew D. Howell, Eric W. Ottesen, Natalia N. Singh, Rachel L. Anderson, Joonbae Seo, Senthilkumar Sivanesan, Elizabeth M. Whitley, Ravindra N. Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/52d3ab15d6f44118a9db9e9a35596a5b
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spelling	oai:doaj.org-article:52d3ab15d6f44118a9db9e9a35596a5b2021-12-02T11:52:24ZTIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy10.1038/s41598-017-07468-22045-2322https://doaj.org/article/52d3ab15d6f44118a9db9e9a35596a5b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07468-2https://doaj.org/toc/2045-2322Abstract Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C +/+) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN exon 7 splicing. TIA1 is reported to be downregulated in obese patients, although it is not known if the effect is gender-specific. We show that female Tia1-knockout (Tia1 −/−) mice gain significant body weight (BW) during early postnatal development. We next examined the effect of Tia1 deletion in novel C +/+/Tia1 −/− mice. Underscoring the opposing effects of Tia1 deletion and low SMN level on BW gain, both C +/+ and C +/+/Tia1 −/− females showed similar BW gain trajectory at all time points during our study. We observed early tail necrosis in C +/+/Tia1 −/− females but not in males. We show enhanced impairment of male reproductive organ development and exacerbation of the C +/+/Tia1 −/− testis transcriptome. Our findings implicate a protein factor as a gender-specific modifier of a mild mouse model of SMA.Matthew D. HowellEric W. OttesenNatalia N. SinghRachel L. AndersonJoonbae SeoSenthilkumar SivanesanElizabeth M. WhitleyRavindra N. SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-18 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew D. Howell Eric W. Ottesen Natalia N. Singh Rachel L. Anderson Joonbae Seo Senthilkumar Sivanesan Elizabeth M. Whitley Ravindra N. Singh TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy
description	Abstract Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C +/+) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN exon 7 splicing. TIA1 is reported to be downregulated in obese patients, although it is not known if the effect is gender-specific. We show that female Tia1-knockout (Tia1 −/−) mice gain significant body weight (BW) during early postnatal development. We next examined the effect of Tia1 deletion in novel C +/+/Tia1 −/− mice. Underscoring the opposing effects of Tia1 deletion and low SMN level on BW gain, both C +/+ and C +/+/Tia1 −/− females showed similar BW gain trajectory at all time points during our study. We observed early tail necrosis in C +/+/Tia1 −/− females but not in males. We show enhanced impairment of male reproductive organ development and exacerbation of the C +/+/Tia1 −/− testis transcriptome. Our findings implicate a protein factor as a gender-specific modifier of a mild mouse model of SMA.
format	article
author	Matthew D. Howell Eric W. Ottesen Natalia N. Singh Rachel L. Anderson Joonbae Seo Senthilkumar Sivanesan Elizabeth M. Whitley Ravindra N. Singh
author_facet	Matthew D. Howell Eric W. Ottesen Natalia N. Singh Rachel L. Anderson Joonbae Seo Senthilkumar Sivanesan Elizabeth M. Whitley Ravindra N. Singh
author_sort	Matthew D. Howell
title	TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy
title_short	TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy
title_full	TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy
title_fullStr	TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy
title_full_unstemmed	TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy
title_sort	tia1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/52d3ab15d6f44118a9db9e9a35596a5b
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TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy

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