Summary of project PR002361
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002361. The data can be accessed directly via it's Project DOI: 10.21228/M8FN8H This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002361 |
| Project DOI: | doi: 10.21228/M8FN8H |
| Project Title: | Muscle-specific Ryanodine Receptor 1 Properties Underlie Limb-Girdle Muscular Dystrophy 2B/R2 Progression |
| Project Summary: | Ryanodine receptor 1 Ca2+ leak is a signal in skeletal muscle, but chronic leak can underlie pathology. Here we show that in healthy male mouse, limb-girdle muscle presents higher sympathetic input, elevated ryanodine receptor 1 basal phosphorylation, Ca2+ leak and mitochondrial Ca2+ content compared to distal leg muscles. These regional differences are consistent with heat generation in resting muscle to maintain core temperature. The dysferlin-null mouse develops severe pathology in the limb-girdle but not leg muscles. Absence of dysferlin disrupts dihydropyridine receptors’ inhibitory control over ryanodine receptor 1 leak, synergistically increasing leak through the already phosphorylated receptor of limb-girdle muscle, altering Ca2+ handling and distribution leading to reactive oxygen species production prior to disease onset. With age, oxidation of Ca2+ -handling proteins in dysferlin-null limb-girdle muscle exacerbated basal Ca2+ movements. Our results show that muscle-specific pathology in dysferlin-null mice is triggered by increased ryanodine receptor 1 Ca2+ leak. |
| Institute: | University of Queensland |
| Department: | School of Biomedical Sciences |
| Last Name: | Launikonis |
| First Name: | Bradley |
| Address: | School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia |
| Email: | b.launikonis@uq.edu.au |
| Phone: | 61 7 3365 4301 |
Summary of all studies in project PR002361
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003784 | Muscle-specific Ryanodine Receptor 1 Properties Underlie Limb-Girdle Muscular Dystrophy 2B/R2 Progression | Mus musculus | University of Queensland | MS | 2025-03-31 | 1 | 101 | Uploaded data (273.4M)* |
