Spontaneous muscular dystrophy caused by a retrotransposal insertion in the mouse laminin α2 chain gene

Besse, Sylvie; Allamand, Valérie; Vilquin, Jean‐Thomas; Li, Zhenlin; Poirier, Christophe; Vignier, Nicolas; Hori, Hisae; Guénet, Jean-Louis; Guicheney, Pascale

doi:10.1016/s0960-8966(02)00278-x

Cited by 21 publications

(15 citation statements)

References 34 publications

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“…SSPN transgenic (SSPN-Tg) mice exhibit a severe phenotype that is much more similar to laminin-deficient muscle (Besse et al, 2003;Guo et al, 2003;Kuang et al, 1998;Miyagoe et al, 1997;Xu et al, 1994). Taken together, our data support a necessary role for SSPN in organizing proteins within the DGC and in assembly of the extracellular matrix.…”

Section: Introductionsupporting

confidence: 59%

“…Laminins represent one of the major components of the extracellular matrix and mutations in the LAMA2 gene, which encodes laminin-␣2 chain, cause congenital MD (Allamand et al, 1997;Helbling-Leclerc et al, 1995;MiyagoeSuzuki et al, 2000). Although the DGC is normally expressed in mouse models with defects in laminin (dy/dy, dy w /dy ; dy = Lama2), the linkage between the extracellular matrix and the cytoskeleton is disrupted (Besse et al, 2003;Guo et al, 2003;Kuang et al, 1998;Miyagoe et al, 1997;Sunada et al, 1994;Xu et al, 1994). We provide data to demonstrate that the extracellular matrix, including laminin, exhibits abnormal structure in phenotypic SSPN-Tg muscle.…”

Section: Discussionmentioning

confidence: 66%

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Disrupted mechanical stability of the dystrophin-glycoprotein complex causes severe muscular dystrophy in sarcospan transgenic mice

Peter

Miller

Crosbie

2007

Journal of Cell Science

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The dystrophin-glycoprotein complex spans the muscle plasma membrane and provides a mechanical linkage between laminin in the extracellular matrix and actin in the intracellular cytoskeleton. Within the dystrophin-glycoprotein complex, the sarcoglycans and sarcospan constitute a subcomplex of transmembrane proteins that stabilize α-dystroglycan, a receptor for laminin and other components of the extracellular matrix. In order to elucidate the function of sarcospan, we generated transgenic mice that overexpress sarcospan in skeletal muscle. Sarcospan transgenic mice with moderate (tenfold) levels of sarcospan overexpression exhibit a severe phenotype that is similar to mouse models of laminin-deficient congenital muscular dystrophy (MD). Sarcospan transgenic mice display severe kyphosis and die prematurely between 6 and 10 weeks of age. Histological analysis reveals that sarcospan expression causes muscle pathology marked by increased muscle fiber degeneration and/or regeneration. Sarcospan transgenic muscle does not display sarcolemma damage, which is distinct from dystrophin- and sarcoglycan-deficient muscular dystrophies. We show that sarcospan clusters the sarcoglycans into insoluble protein aggregates and causes destabilization of α-dystroglycan. Evidence is provided to demonstrate abnormal extracellular matrix assembly, which represents a probable pathological mechanism for the severe and lethal dystrophic phenotype. Taken together, these data suggest that sarcospan plays an important mechanical role in stabilizing the dystrophin-glycoprotein complex.

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Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 66%

Disrupted mechanical stability of the dystrophin-glycoprotein complex causes severe muscular dystrophy in sarcospan transgenic mice

Peter

Miller

Crosbie

2007

Journal of Cell Science

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“…In this regard, overexpression of γ-SG in mouse muscle leads to a muscular dystrophy with similar histopathological features to that observed in both dystrophin-null and γ-SG-null mice. 8 In addition, disturbance of the SG-SSPN complex by SSPN overexpression in muscle of transgenic mice leads to a severe phenotype 9 comparable to that caused by laminin deficiency, 10,11 suggesting that alteration of the equimolar stoichiometry of the sarcoglycans may result in disruption of the entire complex.…”

Section: Introductionmentioning

confidence: 99%

Sox9 Represses α-Sarcoglycan Gene Expression in Early Myogenic Differentiation

Delgado-Olguı́n¹,

Aguillón-Huerta²,

Furlan-Magaril³

et al. 2009

Journal of Molecular Biology

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“…Thus, a major challenge for the future is to understand which types of intracellular signals directly emanate from integrin adhesions, and how these signals are propagated. This requires generation (Bonaldo et al 1998) Severe, early onset muscle weakness, white matter hypodensity, mental retardation LAMA2 (laminin 211) Attachment, migration and organization of myoblasts Dy/Dy (naturally occurring mutant) (Sunada et al 1994) Dy2j/Dy2j (naturally occurring mutant) (Xu et al 1994) DyPas/DyPas (naturally occurring null allele) (Besse et al 2003) Dy3K/Dy3K (KO) (Miyagoe et al 1997) DyW/DyW (hypomorph) (Kuang et al 1998 (Chapman et al 1989) Mdx 52 (deletion of exon 52) (Araki et al 1997) a Ablation of the col6a1 gene. b Mutants recovered from ENU chemical mutagenesis screen.…”

Section: Discussionmentioning

confidence: 99%