| http://purl.uniprot.org/citations/34437302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34437302 | http://www.w3.org/2000/01/rdf-schema#comment | "Myosin binding protein-C slow (sMyBP-C) comprises a subfamily of cytoskeletal proteins encoded by MYBPC1 that is expressed in skeletal muscles where it contributes to myosin thick filament stabilization and actomyosin cross-bridge regulation. Recently, our group described the causal association of dominant missense pathogenic variants in MYBPC1 with an early-onset myopathy characterized by generalized muscle weakness, hypotonia, dysmorphia, skeletal deformities, and myogenic tremor, occurring in the absence of neuropathy. To mechanistically interrogate the etiologies of this MYBPC1-associated myopathy in vivo, we generated a knock-in mouse model carrying the E248K pathogenic variant. Using a battery of phenotypic, behavioral, and physiological measurements spanning neonatal to young adult life, we found that heterozygous E248K mice faithfully recapitulated the onset and progression of generalized myopathy, tremor occurrence, and skeletal deformities seen in human carriers. Moreover, using a combination of biochemical, ultrastructural, and contractile assessments at the level of the tissue, cell, and myofilaments, we show that the loss-of-function phenotype observed in mutant muscles is primarily driven by disordered and misaligned sarcomeres containing fragmented and out-of-register internal membranes that result in reduced force production and tremor initiation. Collectively, our findings provide mechanistic insights underscoring the E248K-disease pathogenesis and offer a relevant preclinical model for therapeutic discovery."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci.insight.147612"xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Zhao R."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Ward C."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Kontrogianni-Konstantopoulos A."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "McDonald K.S."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Stavusis J."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Stains J.P."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Konstantopoulos K."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Vandermeulen J."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Joca H.C."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Geist Hauserman J."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Hanft L."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/author | "Robinett J.C."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/name | "JCI Insight"xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/pages | "e147612"xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/title | "Sarcomeric deficits underlie MYBPC1-associated myopathy with myogenic tremor."xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://purl.uniprot.org/core/volume | "6"xsd:string |
| http://purl.uniprot.org/citations/34437302 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34437302 |
| http://purl.uniprot.org/citations/34437302 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34437302 |
| http://purl.uniprot.org/uniprot/#_G0YZM8-mappedCitation-34437302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34437302 |
| http://purl.uniprot.org/uniprot/#_G0YZM9-mappedCitation-34437302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34437302 |
| http://purl.uniprot.org/uniprot/#_D3YU50-mappedCitation-34437302 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34437302 |