Project description:Laminin (merosin) deficient muscular dystrophy in dy/dy mouse diaphragm muscle, 8 weeks old Experiment Overall Design: 4 normal samples; 4 dystrophic samples; Each sample consists of muscle pooled from 3 mice, thus a total of 12 normal and 12 dystrophic mice were studied
Project description:SUMMARY Congenital muscular dystrophy with laminin á2 chain-deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by decreased muscle tone at birth, reduced movements and contractures. The genetic basis of MDC1A is well-known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin á2 chain-deficient dy3K/dy3K mice, using the multidimensional protein identification technology combined with tandem mass tags. Out of the around 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared to normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin á2 chain-deficient muscle may help to design future anti-fibrotic treatment.
Project description:Canine muscular dystrophy (CXMDJ) is a dog model of the lethal X-linked muscle disorder Duchenne muscular dystrophy (DMD), which is caused by loss of dystrophin. Gene expression profile was analyzed in the diaphragm muscles of normal Beagle dogs and CXMDJ before and 1 hour after initial respiration.
Project description:Canine muscular dystrophy (CXMDJ) is a dog model of the lethal X-linked muscle disorder Duchenne muscular dystrophy (DMD), which is caused by loss of dystrophin. Gene expression profile was analyzed in the diaphragm muscles of normal Beagle dogs and CXMDJ before and 1 hour after initial respiration. Diaphragm were isolated from four groups (normal Beagle dogs and CXMDJ before and 1 hour after initial respiration). Total RNA was purified and prepared to Agilent-021193 Canine (V2) Gene Expression Microarray (Feature Number version) (Agilent Technologies) using Agilkent reagents and protocols. The mRNA levels of differential expressed genes from gene chip analysis were confirmed by quantitative real-time PCR assay.
Project description:The extracellular matrix protein laminin-α2 is essential for preserving the integrity of skeletal muscle fibers during contraction. Its importance is reflected by the severe, congenital LAMA2-related muscular dystrophy (LAMA2 MD) caused by loss-of-function mutations in the LAMA2 gene. While laminin-α2 has an established role in structurally supporting muscle fibers, it remains unclear whether it exerts additional functions that contribute to the maintenance of skeletal muscle integrity. Submitted transcriptomic data represents gene expression profile of control and LAMA2-deficient human myogenic precursor cells derived from induced pluripotent stem cells which was analyzed to better understand the role of laminin-α2 in human cells.
Project description:Diaphragm and hindlimb muscle samples from BL10 or MDX mice treated with L-arginine or untreated. Ages 3/5/9/12 weeks are represented in analysis. Keywords = Muscular dystrophy Keywords = mdx Keywords = DNA microarrays Keywords = L-arginine Keywords = gene expression profiling Keywords: other
