Proteomic analysis of skeletal muscles from wild type and transgenic mice carrying recessive Ryr1 mutations

ABSTRACT: Skeletal muscle is a highly structured and differentiated tissue responsible for voluntary movement and metabolic regulation. Muscles however, are heterogeneous and depending on their location, speed of contraction, fatiguability and function, can be broadly subdivided into fast and slow twitch as well as subspecialized muscles, with each group expressing common as well as specific proteins. Congenital myopathies are a group of non-inflammatory non-dystrophic muscle diseases caused by mutations in a number of genes, leading to a weak muscle phenotype. In most cases specific muscles types are affected, with preferential involvement of fast twitch muscles as well as extraocular and facial muscles. The aim of this study is to compare the proteome of three groups of muscles from wild type and transgenic mice carrying compound heterozygous mutations in Ryr1 identified in a patient with a severe congenital myopathy. Qualitative proteomic analysis was performed by comparing the relative fold change of proteins in fast twitch and slow twitch muscles. Subsequently we compared the proteome of different muscles in wild type and Ryr1 mutant mice. Finally, we applied a quantitative analysis to determine the stoichiometry of the main protein components involved in excitation contraction coupling and calcium regulation. Our results show that recessive Ryr1 mutations do not only cause a change in RyR1 protein content in skeletal muscle, but they are accompanied by profound changes in protein expression in the different muscle types and that the latter effect may be responsible in part, for the weak muscle phenotype observed in patients.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Alexander Schmidt  

LAB HEAD: Alexander Schmidt

PROVIDER: PXD036789 | Pride | 2022-09-27

REPOSITORIES: Pride