Laminin α2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

Guo, Ling; Zhang, X.U.; Kuang, Wen; Xu, Hong; Liu, L.A.; Vilquin, Jean‐Thomas; Miyagoe-Suzuki, Yuko; Takeda, Shin’ichi; Rüegg, Markus A.; Wewer, Ulla M.; Engvall, Eva

doi:10.1016/s0960-8966(02)00266-3

Cited by 75 publications

(85 citation statements)

References 43 publications

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“…From 1994, knock-out mouse or spontaneous mutant mouse strains have been identified as animal models for MDC1A with total and partial deficiency [99][100][101][102][103][104][105] , and experimental therapeutic strategies have been attempted 102,103,[106][107][108][109][110][111][112][113][114][115][116] . In mice, Kuang et al 102,103 were successful in obtaining the expression of a human laminin alpha 2 chain transgene under the regulation of a muscle-specific creatine kinase promoter.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Reed

2009

Arq. Neuro-Psiquiatr.

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-The congenital muscular dystrophies (CMDs) are a group of genetically and clinically heterogeneous hereditary myopathies with preferentially autosomal recessive inheritance, that are characterized by congenital hypotonia, delayed motor development and early onset of progressive muscle weakness associated with dystrophic pattern on muscle biopsy. The clinical course is broadly variable and can comprise the involvement of the brain and eyes. From 1994, a great development in the knowledge of the molecular basis has occurred and the classification of CMDs has to be continuously up dated. In the last number of this journal, we presented the main clinical and diagnostic data concerning the different subtypes of CMD. In this second part of the review, we analyse the main reports from the literature concerning the pathogenesis and the therapeutic perspectives of the most common subtypes of CMD: MDC1A with merosin deficiency, collagen VI related CMDs (Ullrich and Bethlem), CMDs with abnormal glycosylation of alpha-dystroglycan (Fukuyama CMD, Muscleeye-brain disease, Walker Warburg syndrome, MDC1C, MDC1D), and rigid spine syndrome, another much rare subtype of CMDs not related with the dystrophin/glycoproteins/extracellular matrix complex.Key WorDs: congenital muscular dystrophy, MDC1A, collagen VI related disorders, glycosylation of alphadystroglycan, Fukuyama DMC, muscle-eye-brain (MeB) disease, Walker-Warburg syndrome, rigid spine syndrome. distrofia muscular congênita. parte ii: revisão da patogênese e perspectivas terapêuticas resumo -As distrofias musculares congênitas (DMCs) são miopatias hereditárias geralmente, porém não exclusivamente, de herança autossômica recessiva, que apresentam grande heterogeneidade genética e clínica. são caracterizadas por hipotonia muscular congênita, atraso do desenvolvimento motor e fraqueza muscular de início precoce associada a padrão distrófico na biópsia muscular. o quadro clínico, de gravidade variável, pode também incluir anormalidades oculares e do sistema nervoso central. A partir de 1994, os conhecimentos sobre genética e biologia molecular das DMCs progrediram rapidamente, sendo a classificação continuamente atualizada. os aspectos clínicos e diagnósticos dos principais subtipos de DMC foram apresentados no número anterior deste periódico, como primeira parte desta revisão. Nesta segunda parte apresentaremos os principais mecanismos patogênicos e as perspectivas terapêuticas dos subtipos mais comuns de DMC: DMC tipo 1A com deficiência de merosina, DMCs relacionadas com alterações do colágeno VI (Ullrich e Bethlem), e DMCs com anormalidades de glicosilação da alfa-distroglicana (DMC Fukuyama, DMC "Muscle-eye-brain" ou MeB, síndrome de Walker Warburg, DMC tipo 1C, DMC tipo 1D). A DMC com espinha rígida, mais rara e não relacionada com alterações do complexo distrofina-glicoproteínas associadas-matriz extracelular também será abordada quanto aos mesmos aspectos patogênicos e terapêuticos.PAlAVrAs-ChAVes: distrofia muscular congênita, merosina, colágeno VI, glicosila...

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Section: Therapeutic Perspectivesmentioning

confidence: 99%

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Reed

2009

Arq. Neuro-Psiquiatr.

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“…For this reason, we chose to use the genetically more defined laminin-␣2 knockout dy w ͞dy w model, because rapid PCR screening could be used for identification of homozygous (dy w ͞dy w ) neonates. Furthermore, the dy w ͞dy w mice manifest very severe clinical phenotypes and rarely live beyond 2 months of age (6,17,39). The mice are also physically passive and much smaller and thinner than their WT and heterozygote littermates, therefore serving as a clinically relevant model for the evaluation of therapeutic efficacies.…”

Section: Systemic Gene Delivery Improves Multiple Vital Muscles and Hmentioning

confidence: 99%

Amelioration of laminin-α2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin

Qiao

Zhu

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Congenital muscular dystrophy (CMD) is characterized by severe muscle wasting, premature death in early childhood, and lack of effective treatment. Most of the CMD cases are caused by genetic mutations of laminin-␣2, which is essential for the structural integrity of muscle extracellular matrix. Here, we report that somatic gene delivery of a structurally unrelated protein, a miniature version of agrin, functionally compensates for laminin-␣2 deficiency in the murine models of CMD. Adeno-associated virusmediated overexpression of miniagrin restored the structural integrity of myofiber basal lamina, inhibited interstitial fibrosis, and ameliorated dystrophic pathology. Furthermore, systemic gene delivery of miniagrin into multiple vital muscles significantly improved whole body growth and motility and quadrupled the lifespan (50% survival) of the dystrophic mice. Thus, our study demonstrated the efficacy of somatic gene therapy in a mouse model of CMD.adeno-associated virus ͉ integrity ͉ myofiber basal laming ͉ gene therapy

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“…Laminin 211 and 221 are expressed later and are the major laminins of the skeletal muscle basement membrane (Cachaço et al, 2005;Durbeej, 2010). Their presence in the myotube basement membrane is important for myotube stability during contraction, and lack of laminin a2 chain leads to muscle dystrophy (Guo et al, 2003;Huh et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix remodeling accompanies axial muscle development and morphogenesis in the mouse

Deries

Gonçalves

Vaz

et al. 2011

Developmental Dynamics

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Background: Skeletal myogenesis is extensively influenced by the surrounding environment. However, how the extracellular matrix (ECM) affects morphogenesis of muscles is not well understood. Results: We mapped the three-dimensional (3D) organization of fibronectin, tenascin, and laminin by immunofluorescence during early epaxial myogenesis in mouse embryos. We define four stages of dermomyotome/myotome development and reveal the 3D organization of myogenic cells within their ECM during those stages. Fibronectin is abundant in all interstitial tissues, while tenascin is restricted to intersegmental borders. Bundles of fibronectin and tenascin also penetrate into the myotome, possibly promoting myocyte alignment. A laminin matrix delineates the dermomyotome and myotome and undergoes dynamic changes, correlating with key developmental events. Conclusion: Our observations cast new light on how myotomal cells interact with their environment and suggest that, as the segmented myotomes transform into the epaxial muscle masses, the laminin matrix disassembles and myocytes use the abundant fibronectin matrix to reach their final organization. Developmental Dynamics 241:350-364,

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Laminin α2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

Cited by 75 publications

References 43 publications

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

Amelioration of laminin-α2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin

Extracellular matrix remodeling accompanies axial muscle development and morphogenesis in the mouse

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