Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genotyping of autosomal recessive type of limb-girdle muscular dystrophies

ABSTRACT: 26 limb-girdle muscular dystrophy patients from Latvia and 34 patients from Lithuania with clinical symptoms of limb-girdle muscular dystrophies, along with 204 healthy unrelated controls were genotyped for 96 most frequent known limb-girdle muscular dystrophies causing mutations for the region, using VeraCode GoldenGate system. More information can be found in article Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies in BMC Musculoskeletal Disorders by I. Inashkina et al.

ORGANISM(S): Homo sapiens

SUBMITTER: Janis Stavusis

PROVIDER: E-MTAB-4662 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Limb-girdle muscular dystrophies (LGMD) is a group of muscle diseases characterized by pro-gressive muscle weakness and muscular atrophy of proximal muscles. Limb-girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a specific LGMD caused by a gene mutation encoding the calcium-dependent neutral cysteine protease calpain-3 (CAPN3). In our previous study, a novel compound heterozygous mutation, c.635T>C causing missense mu-tation of p.Leu212Pro, was identified in LGMDR1 patients. For the investigation of the molecular mechanism for muscular dystrophy, LGMDR1 CAPN3-point-mutation mouse model was pre-pared by injecting into fertilized eggs of C57 mice the following: in vitro transcribed Cas9 mRNA, sgRNA for mutation sites, and homologous fragments. The LGMDR1 models displayed a mild and slow malnutrition phenotype until 10 months old. Western blot and immunofluorescence assay also showed that the expression level of CAPN3 protein in muscle tissue of mutant mice was similar to that of wild-type mice. Pathological results revealed that a few inflammatory cells infiltrated the endomyocytes of some homozygous mice at 10 months of age. Compared with wild-type mice, motor function was not significantly impaired in CAPN3 mutant mice. Interest-ingly, we found that the arrangement and ultrastructural alterations of mitochondria in the muscular tissue of homozygous mice at the electron microscopy level. Then, muscle regeneration of LGMDR1 was simulated using Cardiotoxin (CTX) to induce muscle necrosis and regeneration to trigger the injury modification process. A large number of inflammatory cells and damaged myofibers were observed in both mutant mice and wild type mice 3 and 6 days after CTX treat-ment. Fifteen and twenty-one days after treatment, the repair of diseased mice was significantly worse than that of control mice. RNA-seq results demonstrated that the expression of mito-chondrial-related functional genes was significantly down-regulated in mutant mice. Taken to-gether, our results strongly suggest that LGMDR1 mouse model with a novel c.635T >C mutation in CAPN3 gene was significant disfunction in muscle injury repair through impairing the mito-chondrion.

Dataset Information

Genotyping of autosomal recessive type of limb-girdle muscular dystrophies

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets