ArticleHuman molecular genetics2014
The transgenic expression of LARGE exacerbates the muscle phenotype of dystroglycanopathy mice.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Malformations of Core M3 on α-Dystroglycan Are the Leading Cause of Dystroglycanopathies.Journal of molecular neuroscience : MN · 2025Review
- Break Down of the Complexity and Inconsistency Between Levels of Matriglycan and Disease Phenotype in FKRP-Related Dystroglycanopathies: A Review and Model of Interpretation.Journal of neuromuscular diseases · 2024Review
- Dystroglycanopathy: From Elucidation of Molecular and Pathological Mechanisms to Development of Treatment Methods.International journal of molecular sciences · 2021Review
- A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy.Cell reports · 2021Article
- GMPPA defects cause a neuromuscular disorder with α-dystroglycan hyperglycosylation.The Journal of clinical investigation · 2021Article
- Fukutin-Related Protein: From Pathology to Treatments.Trends in cell biology · 2021Review
- The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy.Disease models & mechanisms · 2018Review
- Dose-Dependent Effects of FKRP Gene-Replacement Therapy on Functional Rescue and Longevity in Dystrophic Mice.Molecular therapy. Methods & clinical development · 2018Article
- Treating pediatric neuromuscular disorders: The future is now.American journal of medical genetics. Part A · 2018Review
- AAV-mediated transfer of FKRP shows therapeutic efficacy in a murine model but requires control of gene expression.Human molecular genetics · 2017Article
- Article
- 212th ENMC International Workshop: Animal models of congenital muscular dystrophies, Naarden, The Netherlands, 29-31 May 2015.Neuromuscular disorders : NMD · 2016Article
- Article
- Prenatal muscle development in a mouse model for the secondary dystroglycanopathies.Skeletal muscle · 2016Article
- How much dystrophin is enough: the physiological consequences of different levels of dystrophin in the mdx mouse.Human molecular genetics · 2015Article
- Matriglycan: a novel polysaccharide that links dystroglycan to the basement membrane.Glycobiology · 2015Review
- Fukutin is prerequisite to ameliorate muscular dystrophic phenotype by myofiber-selective LARGE expression.Scientific reports · 2015Article
- Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy.BioMed research international · 2015Review
- What do mouse models of muscular dystrophy tell us about the DAPC and its components?International journal of experimental pathology · 2014Review
- miRNA-based buffering of the cobblestone-lissencephaly-associated extracellular matrix receptor dystroglycan via its alternative 3'-UTR.Nature communications · 2014Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in fukutin-related protein (FKRP) underlie a group of muscular dystrophies associated with the hypoglycosylation of α-dystroglycan (α-DG), a proportion of which show central nervous system involvement. Our original FKRP knock-down mouse (FKRP(KD)) replicated many of the characteristics seen in patients at the severe end of the dystroglycanopathy spectrum but died perinatally precluding its full phenotyping and use in testing potential therapies. We have now overcome this by crossing FKRP(KD) mice with those expressing Cre recombinase under the Sox1 promoter. Owing to our original targeting strategy, this has resulted in the restoration of Fkrp levels in the central nervous system but not the muscle, thereby generating a new model (FKRP(MD)) which develops a progressive muscular dystrophy resembling what is observed in limb girdle muscular dystrophy. Like-acetylglucosaminyltransferase (LARGE) is a bifunctional glycosyltransferase previously shown to hyperglycosylate α-DG. To investigate the therapeutic potential of LARGE up-regulation, we have now crossed the FKRP(MD) line with one overexpressing LARGE and show that, contrary to expectation, this results in a worsening of the muscle pathology implying that any future strategies based upon LARGE up-regulation require careful management.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.