Gene replacement rescues severe muscle pathology and prolongs survival in myotubularin-deficient mice and dogs.
نویسندگان
چکیده
Department of Rehabilitation Medicine, Institute for Stem Cell and Regenerative Medicine, School of Medicine, University of Washington, Seattle, Washington 98109, USA; The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; Généthon, INSERM UMR 951, Evry, France Correspondence to: Martin K. Childers. Department of Rehabilitation Medicine, Institute for Stem Cell and Regenerative Medicine, School of Medicine, University of Washington, Seattle, Washington 98109, USA. Email: [email protected].
منابع مشابه
Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy.
No effective treatment exists for patients with X-linked myotubular myopathy (XLMTM), a fatal congenital muscle disease caused by deficiency of the lipid phosphatase, myotubularin. The Mtm1δ4 and Mtm1 p.R69C mice model severely and moderately symptomatic XLMTM, respectively, due to differences in the degree of myotubularin deficiency. Contractile function of intact extensor digitorum longus (ED...
متن کاملGene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy.
Loss-of-function mutations in the myotubularin gene (MTM1) cause X-linked myotubular myopathy (XLMTM), a fatal, congenital pediatric disease that affects the entire skeletal musculature. Systemic administration of a single dose of a recombinant serotype 8 adeno-associated virus (AAV8) vector expressing murine myotubularin to Mtm1-deficient knockout mice at the onset or at late stages of the dis...
متن کاملSkeletal Muscle Pathology in X-Linked Myotubular Myopathy: Review With Cross-Species Comparisons
X-linked myotubular myopathy (XLMTM) is a devastating, rare, congenital myopathy caused by mutations in the MTM1 gene, resulting in a lack of or dysfunction of the enzyme myotubularin. This leads to severe perinatal weakness and distinctive muscle pathology. It was originally thought that XLMTM was related to developmental arrest in myotube maturation; however, the generation and characterizati...
متن کاملAAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis
Myotubular myopathy (XLMTM, OMIM 310400) is a severe congenital muscular disease due to mutations in the myotubularin gene (MTM1) and characterized by the presence of small myofibers with frequent occurrence of central nuclei. Myotubularin is a ubiquitously expressed phosphoinositide phosphatase with a muscle-specific role in man and mouse that is poorly understood. No specific treatment exists...
متن کاملModeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype.
X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin. The Mtm1 knockout (KO) mouse has a severe phenotype and its short lifespan (8 weeks) makes it a challenge to use as a model in the testing of certain preclinical therapeutics. Many MTM patients succumb early in life, but...
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ورودعنوان ژورنال:
- Annals of translational medicine
دوره 3 17 شماره
صفحات -
تاریخ انتشار 2015