Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

A New Mouse Model of Limb-Girdle Muscular Dystrophy Type 2I Homozygous for the Common L276I Mutation Mimicking the Mild Phenotype in Humans

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Molecular Characterization of the Danish Prion Diseases Cohort With Special Emphasis on Rare and Unique Cases

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A Novel Eight Octapeptide Repeat Insertion in PRNP Causing Prion Disease in a Danish Family

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The cGMP-Degrading Enzyme Phosphodiesterase-5 (PDE5) in Cerebral Small Arteries of Older People

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Absence of p.R50X Pygm read-through in McArdle disease cellular models

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Hydroxylated Long-Chain Acylcarnitines are Biomarkers of Mitochondrial Myopathy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Exercise therapy for muscle and lower motor neuron diseases

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Limb-girdle muscular dystrophy type 2I (LGMD2I) is caused by mutations in the Fukutin-related protein (FKRP) gene, leading to inadequate glycosylation of α-dystroglycan, an important protein linking the extracellular matrix to the cytoskeleton. We created a mouse model of the common FKRP L276I mutation and a hemizygous FKRP L276I knockout model. We studied histopathology and protein expression in the models at different ages and found that homozygous FKRP L276I mice developed a mild progressive myopathy with increased muscle regeneration and fibrosis starting from 1 year of age. This was likely caused by progressive loss of α-dystroglycan-specific glycosylation, which was decreased by 78% at 20 months. The homozygous FKRP knockout was embryonic lethal, but the hemizygous L276I model resembled the homozygous FKRP L276I model at comparable ages. These models emphasize the importance of FKRP in maintaining proper glycosylation of α-dystroglycan. The mild progression in the homozygous FKRP L276I model resembles that in patients with LGMD2I who are homozygous for the L276I mutation. This animal model could, therefore, be relevant for understanding the pathophysiology of and developing a treatment strategy for the human disorder.

OriginalsprogEngelsk
TidsskriftJournal of Neuropathology and Experimental Neurology
Vol/bind74
Udgave nummer12
Sider (fra-til)1137-46
Antal sider10
ISSN0022-3069
DOI
StatusUdgivet - dec. 2015

ID: 46039671