ArticleAging cell2010
The I4895T mutation in the type 1 ryanodine receptor induces fiber-type specific alterations in skeletal muscle that mimic premature aging.
Article in Aging cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Molecular Insights into Central Core Disease: Proteomic Signatures and Potential Therapeutic Biomarkers in RYR1 I4895T Mice.International journal of molecular sciences · 2025Article
- Limited pre-clinical relevance of the heterozygous RYR1-I4895T/+ mouse model due to its mild phenotype.Journal of neuromuscular diseases · 2025Article
- Constitutive assembly of Ca2+ entry units in soleus muscle from calsequestrin knockout mice.The Journal of general physiology · 2022Article
- Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies.The Journal of general physiology · 2022Review
- Endurance exercise attenuates juvenile irradiation-induced skeletal muscle functional decline and mitochondrial stress.Skeletal muscle · 2022Article
- Altered CaMetabolites · 2021Review
- Pathological mechanisms of vacuolar aggregate myopathy arising from a Casq1 mutation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy.Cell death and differentiation · 2021Article
- Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990-2019.Orphanet journal of rare diseases · 2020Article
- Cored in the act: the use of models to understand core myopathies.Disease models & mechanisms · 2019Review
- Elongated mitochondrial constrictions and fission in muscle fatigue.Journal of cell science · 2018Article
- Inositol trisphosphate receptor-mediated Ca2+ signalling stimulates mitochondrial function and gene expression in core myopathy patients.Human molecular genetics · 2018Article
- A chemical chaperone improves muscle function in mice with a RyR1 mutation.Nature communications · 2017Article
- Skeletal Muscle Microalterations in Patients Carrying Malignant Hyperthermia-Related Mutations of the e-c Coupling Machinery.European journal of translational myology · 2016Article
- Age-dependent uncoupling of mitochondria from Ca2⁺ release units in skeletal muscle.Oncotarget · 2015Article
- Editorial: The EJTM Special "Mobility in Elderly".European journal of translational myology · 2015Article
- Dyad content is reduced in cardiac myocytes of mice with impaired calmodulin regulation of RyR2.Journal of muscle research and cell motility · 2015Article
- The disorders of the calcium release unit of skeletal muscles: what have we learned from mouse models?Journal of muscle research and cell motility · 2015Review
- Article
- The Ejtm Specials "The Long-Term Denervated Muscle".European journal of translational myology · 2014Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The I4898T (IT) mutation in type 1 ryanodine receptor (RyR1), the Ca(2+) release channel of the sarcoplasmic reticulum (SR) is linked to a form of central core disease (CCD) in humans and results in a nonleaky channel and excitation-contraction uncoupling. We characterized age-dependent and fiber-type-dependent alterations in muscle ultrastructure, as well as the magnitude and spatiotemporal properties of evoked Ca(2+) release in heterozygous Ryr1(I4895T/WT) (IT/+) knock-in mice on a mixed genetic background. The results indicate a classical but mild CCD phenotype that includes muscle weakness and the presence of mitochondrial-deficient areas in type I fibers. Electrically evoked Ca(2+) release is significantly reduced in single flexor digitorum brevis (FDB) fibers from young and old IT/+ mice. Structural changes are strongly fiber-type specific, affecting type I and IIB/IIX fibers in very distinct ways, and sparing type IIA fibers. Ultrastructural alterations in our IT/+ mice are also present in wild type, but at a lower frequency and older ages, suggesting that the disease mutation on the mixed background promotes an acceleration of normal age-dependent changes. The observed functional and structural alterations and their similarity to age-associated changes are entirely consistent with the known properties of the mutated channel, which result in reduced calcium release as is also observed in normal aging muscle. In strong contrast to these observations, a subset of patients with the analogous human heterozygous mutation and IT/+ mice on an inbred 129S2/SvPasCrl background exhibit a more severe disease phenotype, which is not directly consistent with the mutated channel properties.
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