Murine muscular dystrophy caused by a mutation in the laminin α2 (Lama2) gene

@article{Xu1994MurineMD,
  title={Murine muscular dystrophy caused by a mutation in the laminin $\alpha$2 (Lama2) gene},
  author={Hong Xu and Xiao-Rong Wu and Ulla M. Wewer and E O Engvall},
  journal={Nature Genetics},
  year={1994},
  volume={8},
  pages={297-302}
}
The classic murine muscular dystrophy strain, dy, was first described almost 40 years ago. We have identified the molecular basis of an allele of dy, called dy 2J, by detecting a mutation in the laminin α2 chain gene — the first identified mutation in laminin-2. The G to A mutation in a splice site consensus sequence causes abnormal splicing and expression of multiple mRNAs. One mRNA is translated into an α2 polypeptide with a deletion in domain VI. The truncated protein apparently lacks… Expand
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TLDR
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References

SHOWING 1-10 OF 39 REFERENCES
Muscular dystrophy in the mouse caused by an allele at the dy-locus.
TLDR
A progressive hereditary myopathy of mice caused by a second allele, dy 2J, at the dy -locus is described, which is milder than the original muscular dystrophy, and both afflicted males and females have bred. Expand
Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain gene to dy locus.
TLDR
It is demonstrated that merosin is a native ligand for alpha-dystroglycan, an extracellular component of the dystrophin-glycoprotein complex, and suggested that a disruption of the link between alpha-dieselcan and Merosin may be involved in the pathogenesis of muscle degeneration and peripheral neuropathy in dy mice. Expand
Mutations in the γ2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa
TLDR
The data implicate mutations in the laminin γ2 chain gene (LAMC2) in some forms of JEB, which is an autosomal recessive disorder characterized by blister formation within the dermal–epidermal basement membrane. Expand
Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse.
TLDR
The dy mouse may provide a model for autosomal muscular dystrophies in humans and facilitate studies of functions of M-laminin, suggesting that a mutation in the M-chain gene causes the muscular dystrophy in dy/dy mice. Expand
Comparison of dy and dy2J , Two Alleles Expressing Forms of Muscular Dystrophy in the Mouse
  • A. D. Macpike, H. Meier
  • Medicine
  • Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine
  • 1976
Summary The muscular dystrophies caused by dy and dy 2J on a C57BL/6J genetic background are similar in quality. At 1 month, slight differences occur in distribution of the muscle lesions, diffuseExpand
Localization of merosin-negative congenital muscular dystrophy to chromosome 6q2 by homozygosity mapping.
TLDR
Following the discovery of merosin deficiency in some CMD cases, a CMD gene in a 16 cM region of chromosome 6q2 in the region of the laminin M chain gene is localized to chromosome 9q31-q33. Expand
Congenital muscular dystrophy with merosin deficiency.
TLDR
A specific absence of merosin, the laminin M chain, is observed in 13 patients affected by classical non-Japanese form of congenital muscular dystrophy, which allows the precise identification of a particular form of Congenital muscular Dystrophy and gives a clue to understanding its molecular pathogenesis. Expand
Abnormal localization of laminin subunits in muscular dystrophies
TLDR
In FCMD muscle, a significant reduction of laminin M (merosin; a striated muscle specific basal lamina-associated protein) is found with approximately 26% of levels seen in controls by quantitative immunofluorescence, which may implicate a primary or central role for the basalLamina in FC MD muscle. Expand
Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the γ2 subunit of nicein/kalinin (LAMININ–5)
TLDR
The H–JEB kindreds have linked Herlitz's junctional epidermolysis bullosa to the gene (LAMC2) encoding the γ2 subunit of nicein/kalinin, an isolaminin expressed by basal keratinocytes, and the segregation of the mutated allele implicates the mutation in the pathology of the disorder and corroborates the linkage results. Expand
Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31–33
TLDR
Twenty–one FCMD families, 13 of them with consanguineous marriages, were analysed by genetic linkage analyses with polymorphic microsatellite markers to map the FCMD gene, and these markers represent important resources for the identification of a gene responsible for FCMD. Expand
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