Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.

<h4>Objective</h4>HIBM (Hereditary Inclusion Body Myopathy) is a recessive hereditary disease characterized by adult-onset, slowly progressive muscle weakness sparing the quadriceps. It is caused by a single missense mutation of each allele of the UDP-N-acetylglucosamine 2-epimerase/N-ac...

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Autores principales:	Thomas Paccalet, Zoé Coulombe, Jacques P Tremblay
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/baa8b396f3554e9183633ee5484f1c19
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spelling	oai:doaj.org-article:baa8b396f3554e9183633ee5484f1c192021-11-25T06:24:43ZGanglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.1932-620310.1371/journal.pone.0010055https://doaj.org/article/baa8b396f3554e9183633ee5484f1c192010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20383336/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>HIBM (Hereditary Inclusion Body Myopathy) is a recessive hereditary disease characterized by adult-onset, slowly progressive muscle weakness sparing the quadriceps. It is caused by a single missense mutation of each allele of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, a bifunctional enzyme catalyzing the first two steps of sialic acid synthesis in mammals. However, the mechanisms and cellular pathways affected by the GNE mutation and causing the muscle weakness could not be identified so far. Based on recent evidence in literature, we investigated a new hypothesis, i.e. the involvement in the disease of the GM3 ganglioside, a specific glycolipid implicated in muscle cell proliferation and differentiation.<h4>Methods</h4>qRT-PCR analysis of St3gal5 (GM3 synthase) gene expression and HPLC quantification of GM3 ganglioside were conducted on muscle tissue from a mouse model of HIBM harboring the M712T mutation of GNE (Gne(M712T/M712T) mouse) vs control mice (Gne(+/+) mouse).<h4>Results</h4>St3gal5 mRNA levels were significantly lower in Gne(M712T/M712T) mouse muscles vs Gne(+/+) mouse muscles (64.41%+/-10% of Gne(+/+) levels). GM3 ganglioside levels showed also a significant decrease in Gne(M712T/M712T) mouse muscle compared to Gne(+/+) mouse muscle (18.09%+/-5.33% of Gne(+/+) levels). Although these Gne(M712T/M712T) mice were described to suffer severe glomerular proteinuria, no GM3 alterations were noted in kidneys, highlighting a tissue specific alteration of gangliosides.<h4>Conclusion</h4>The M712T mutation of GNE hampers the muscle ability to synthesize normal levels of GM3. This is the first time that a mutation of GNE can be related to the molecular pathological mechanism of HIBM.Thomas PaccaletZoé CoulombeJacques P TremblayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10055 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas Paccalet Zoé Coulombe Jacques P Tremblay Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.
description	<h4>Objective</h4>HIBM (Hereditary Inclusion Body Myopathy) is a recessive hereditary disease characterized by adult-onset, slowly progressive muscle weakness sparing the quadriceps. It is caused by a single missense mutation of each allele of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, a bifunctional enzyme catalyzing the first two steps of sialic acid synthesis in mammals. However, the mechanisms and cellular pathways affected by the GNE mutation and causing the muscle weakness could not be identified so far. Based on recent evidence in literature, we investigated a new hypothesis, i.e. the involvement in the disease of the GM3 ganglioside, a specific glycolipid implicated in muscle cell proliferation and differentiation.<h4>Methods</h4>qRT-PCR analysis of St3gal5 (GM3 synthase) gene expression and HPLC quantification of GM3 ganglioside were conducted on muscle tissue from a mouse model of HIBM harboring the M712T mutation of GNE (Gne(M712T/M712T) mouse) vs control mice (Gne(+/+) mouse).<h4>Results</h4>St3gal5 mRNA levels were significantly lower in Gne(M712T/M712T) mouse muscles vs Gne(+/+) mouse muscles (64.41%+/-10% of Gne(+/+) levels). GM3 ganglioside levels showed also a significant decrease in Gne(M712T/M712T) mouse muscle compared to Gne(+/+) mouse muscle (18.09%+/-5.33% of Gne(+/+) levels). Although these Gne(M712T/M712T) mice were described to suffer severe glomerular proteinuria, no GM3 alterations were noted in kidneys, highlighting a tissue specific alteration of gangliosides.<h4>Conclusion</h4>The M712T mutation of GNE hampers the muscle ability to synthesize normal levels of GM3. This is the first time that a mutation of GNE can be related to the molecular pathological mechanism of HIBM.
format	article
author	Thomas Paccalet Zoé Coulombe Jacques P Tremblay
author_facet	Thomas Paccalet Zoé Coulombe Jacques P Tremblay
author_sort	Thomas Paccalet
title	Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.
title_short	Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.
title_full	Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.
title_fullStr	Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.
title_full_unstemmed	Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.
title_sort	ganglioside gm3 levels are altered in a mouse model of hibm: gm3 as a cellular marker of the disease.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/baa8b396f3554e9183633ee5484f1c19
work_keys_str_mv	AT thomaspaccalet gangliosidegm3levelsarealteredinamousemodelofhibmgm3asacellularmarkerofthedisease AT zoecoulombe gangliosidegm3levelsarealteredinamousemodelofhibmgm3asacellularmarkerofthedisease AT jacquesptremblay gangliosidegm3levelsarealteredinamousemodelofhibmgm3asacellularmarkerofthedisease
_version_	1718413767508754432

Ganglioside GM3 levels are altered in a mouse model of HIBM: GM3 as a cellular marker of the disease.

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