ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Mice expressing T4826I-RYR1 are viable but exhibit sex- and genotype-dependent susceptibility to malignant hyperthermia and muscle damage.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 80 citations in OpenAlex.
- Mitochondrial bioenergetics and intracellular calcium concentration in primary myotubes from mouse models of malignant hyperthermia.British journal of anaesthesia · 2026Article
- RyR1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anabolic androgenic steroids and illicit drugs as potential modulating factors in malignant hyperthermia: a case series.Anaesthesiology intensive therapy · 2025Article
- Advances in malignant hyperthermia: novel insights into heat-induced CaJournal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2025Review
- An Association between OXPHOS-Related Gene Expression and Malignant Hyperthermia Susceptibility in Human Skeletal Muscle Biopsies.International journal of molecular sciences · 2024Article
- Two zebrafish cacna1s loss-of-function variants provide models of mild and severe CACNA1S-related myopathy.Human molecular genetics · 2024Article
- Article
- Trans-scale thermal signaling in biological systems.Journal of biochemistry · 2023Review
- Gene×environment interactions in autism spectrum disorders.Current topics in developmental biology · 2023Review
- Development of Ryanodine Receptor (RyR) Inhibitors for Skeletal Muscle and Heart Diseases.Juntendo Iji zasshi = Juntendo medical journal · 2023Article
- Mice with R2509C-RYR1 mutation exhibit dysfunctional Ca2+ dynamics in primary skeletal myocytes.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
- Correlation of Phenotype-Genotype and Protein Structure inFrontiers in neurology · 2022Article
- A novel RyR1-selective inhibitor prevents and rescues sudden death in mouse models of malignant hyperthermia and heat stroke.Nature communications · 2021Article
- Unravelling the unseen metabolic changes in patients with malignant hyperthermia.Canadian journal of anaesthesia = Journal canadien d'anesthesie · 2021Article
- Molecular Modification of Transient Receptor Potential Canonical 6 Channels Modulates Calcium Dyshomeostasis in a Mouse Model Relevant to Malignant Hyperthermia.Anesthesiology · 2021Article
- T lymphocytes from malignant hyperthermia-susceptible mice display aberrations in intracellular calcium signaling and mitochondrial function.Cell calcium · 2021Article
- Sex and Genotype Modulate the Dendritic Effects of Developmental Exposure to a Human-Relevant Polychlorinated Biphenyls Mixture in the Juvenile Mouse.Frontiers in neuroscience · 2021Article
- Developmental Exposure to a Human-Relevant Polychlorinated Biphenyl Mixture Causes Behavioral Phenotypes That Vary by Sex and Genotype in Juvenile Mice Expressing Human Mutations That Modulate Neuronal Calcium.Frontiers in neuroscience · 2021Article
- From Mice to Humans: An Overview of the Potentials and Limitations of Current Transgenic Mouse Models of Major Muscular Dystrophies and Congenital Myopathies.International journal of molecular sciences · 2020Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutation T4825I in the type 1 ryanodine receptor (RYR1(T4825I/+)) confers human malignant hyperthermia susceptibility (MHS). We report a knock-in mouse line that expresses the isogenetic mutation T4826I. Heterozygous RYR1(T4826I/+) (Het) or homozygous RYR1(T4826I/T4826I) (Hom) mice are fully viable under typical rearing conditions but exhibit genotype- and sex-dependent susceptibility to environmental conditions that trigger MH. Hom mice maintain higher core temperatures than WT in the home cage, have chronically elevated myoplasmic[Ca(2+)](rest), and present muscle damage in soleus with a strong sex bias. Mice subjected to heat stress in an enclosed 37°C chamber fail to trigger MH regardless of genotype, whereas heat stress at 41°C invariably triggers fulminant MH in Hom, but not Het, mice within 20 min. WT and Het female mice fail to maintain euthermic body temperature when placed atop a bed whose surface is 37°C during halothane anesthesia (1.75%) and have no hyperthermic response, whereas 100% Hom mice of either sex and 17% of the Het males develop fulminant MH. WT mice placed on a 41°C bed maintain body temperature while being administered halothane, and 40% of the Het females and 100% of the Het males develop fulminant MH within 40 min. Myopathic alterations in soleus were apparent by 12 mo, including abnormally distributed and enlarged mitochondria, deeply infolded sarcolemma, and frequent Z-line streaming regions, which were more severe in males. These data demonstrate that an MHS mutation within the S4-S5 cytoplasmic linker of RYR1 confers genotype- and sex-dependent susceptibility to pharmacological and environmental stressors that trigger fulminant MH and promote myopathy.
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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.