Gene expression analyses in X-linked myotubular myopathy.

Abstract

BACKGROUND:

X-linked myotubular myopathy (XLMTM) is a severe congenital disorder characterized by marked muscle weakness and hypotonia. Myotubularin, the protein product of the causative gene, MTM1, is thought to be a phosphatase for phosphatidylinositol-3-phosphate and may be involved in membrane trafficking. Analysis of MTM1 knocked-out mice indicates that the characteristic small fibers in XLMTM muscles are due to atrophy rather than hypoplasia.

OBJECTIVE:

To characterize gene expression profiling of skeletal muscles with XLMTM.

METHOD:

The authors analyzed the expression of more than 4,200 genes in skeletal muscles from eight patients with XLMTM using their custom cDNA microarray.

RESULTS:

In XLMTM, gene expression analysis revealed pathognomonic upregulation of transcripts for cytoskeletal and extracellular matrix proteins within or around atrophic myofibers.

CONCLUSION:

Remodeling of cytoskeletal and extracellular architecture appears to contribute to atrophy and intracellular organelle disorganization in XLMTM myofibers.

• Authors: S Noguchi, M Fujita, K Murayama, R Kurokawa, I Nishino
• Journal: Neurology (Neurology) Vol. 65 Issue 5 Pg. 732-7 (Sep 13 2005) ISSN: 1526-632X [Electronic] United States
• PMID: 16157907 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cytoskeletal Proteins
• Extracellular Matrix Proteins
• RNA, Messenger

Topics

• Cytoskeletal Proteins (genetics, metabolism)
• Cytoskeleton (genetics, metabolism, pathology)
• Extracellular Matrix (genetics, metabolism, pathology)
• Extracellular Matrix Proteins (genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Developmental (genetics)
• Genetic Diseases, X-Linked (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Immunohistochemistry
• Infant
• Infant, Newborn
• Muscle Fibers, Skeletal (metabolism, pathology)
• Muscle, Skeletal (metabolism, pathology, physiopathology)
• Muscular Atrophy (genetics, metabolism, physiopathology)
• Myopathies, Structural, Congenital (genetics, metabolism, physiopathology)
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger (genetics, metabolism)
• Up-Regulation (genetics)