Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro

被引：32

作者：

Miyagoe-Suzuki, Yuko ^{[1
]}

Masubuchi, Nami ^{[1
,2
]}

Miyamoto, Kaori ^{[1
,2
]}

Wada, Michiko R. ^{[1
]}

Yuasa, Shigeki ^{[3
]}

Saito, Fumiaki ^{[4
]}

Matsumura, Kiichiro ^{[4
]}

Kanesaki, Hironori ^{[5
]}

Kudo, Akira ^{[5
]}

Manya, Hiroshi ^{[6
]}

Endo, Tamao ^{[6
]}

Takeda, Shin'ichi ^{[1
]}

机构：

[1] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mol Therapy, Tokyo 1878502, Japan

[2] Kitasato Univ, Sch Sci, Dept Biosci, Kanagawa 2288555, Japan

[3] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Ultrastruct Res, Tokyo 1878502, Japan

[4] Teikyo Univ, Sch Med, Dept Neurol & Neurosci, Itabashi Ku, Tokyo 1738605, Japan

[5] Tokyo Inst Technol, Dept Biol Informat, Yokohama, Kanagawa 2268501, Japan

[6] Fdn Res Aging & Promot Human Welf, Tokyo Metropolitan Inst Gerontol, Glycobiol Res Grp, Itabashi Ku, Tokyo 1730015, Japan

来源：

MECHANISMS OF DEVELOPMENT | 2009年 / 126卷 / 3-4期

关键词：

POMGnT1; Muscle-eye-brain disease; Satellite cells; Skeletal muscle; alpha-Dystroglycan; Glycosylation; Laminin; DYSTROPHIN-ASSOCIATED GLYCOPROTEINS; CONGENITAL MUSCULAR-DYSTROPHIES; EYE-BRAIN DISEASE; SKELETAL-MUSCLE; SATELLITE CELLS; DYSTROGLYCAN; HYPERTROPHY; DISRUPTION; EXPRESSION; MICE;

D O I：

10.1016/j.mod.2008.12.001

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Protein O-linked mannose beta 1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) is an enzyme that transfers N-acetylglucosamine to O-mannose of glycoproteins. Mutations of the POMGnT1 gene cause muscle-eye-brain (MEB) disease. To obtain a better understanding of the pathogenesis of MEB disease, we mutated the POMGnT1 gene in mice using a targeting technique. The mutant muscle showed aberrant glycosylation of alpha-DG, and alpha-DG from mutant muscle failed to bind laminin in a binding assay. POMGnT1(-/-) muscle showed minimal pathological changes with very low-serum creatine kinase levels, and had normally formed muscle basal lamina, but showed reduced muscle mass, reduced numbers of muscle fibers, and impaired muscle regeneration. Importantly, POMGnT1(-/-) satellite cells proliferated slowly, but efficiently differentiated into multinuclear myotubes in vitro. Transfer of a retrovirus vector-mediated POMGnT1 gene into POMGnT1(-/-) myoblasts completely restored the glycosylation of alpha-DG, but proliferation of the cells was not improved. Our results suggest that proper glycosylation of alpha-DG is important for maintenance of the proliferative activity of satellite cells in vivo. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：107 / 116

页数：10

共 26 条

[11] Breaches of the pial basement membrane and disappearance of the glia limitans during development underlie the cortical lamination defect in the mouse model of muscle-eye-brain disease [J].