Expression profiling with progression of dystrophic change in dysferlin-deficient mice (SJL)

• Published in: Neuroscience research Vol. 52; no. 1; pp. 47 - 60
• Main Authors: Suzuki, Naoki, Aoki, Masashi, Hinuma, Yuji, Takahashi, Toshiaki, Onodera, Yoshiaki, Ishigaki, Aya, Kato, Masaaki, Warita, Hitoshi, Tateyama, Maki, Itoyama, Yasuto
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.05.2005
• Subjects: Animals; Blotting, Western; C2 domain; Disease Models, Animal; Dysferlin; Gene Expression Profiling; Male; Membrane Proteins - deficiency; Mice; Mice, Mutant Strains; Microarray; Miyoshi myopathy; Muscle Proteins - deficiency; Muscle, Skeletal - physiology; Muscular Dystrophies, Limb-Girdle - genetics; Muscular dystrophy; Oligonucleotide Array Sequence Analysis; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; SJL mouse; Tnnt2; GTP; CARP; cardiac atria; HRP; developmentally down-regulated gene 4-like; MHC; NEDD4L; mRNA; VLDLR; Microarray; Muscular dystrophy; Neu2; alkali; RT-PCR; Miyoshi myopathy; cDNA; TGF-beta1; Cxcl; LGMD2B; Scya; Timp; MM; PBS; Myla; Rrad; Mmp3; Dysferlin; EAE; IGF2; C2 domain; cRNA; Cspg2; SDS-PAGE; MIP; OSF2; SJL mouse; nNOS; MCP
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2005.01.006

The SJL mouse is a model for human dysferlinopathy (limb-girdle muscular dystrophy type 2B and Miyoshi myopathy). We used cDNA microarrays to compare the expression profiles of 10,012 genes in control and SJL quadriceps femoris muscles in order to find genes involved in the degeneration and regeneration process and in dysferlin's functional network. Many genes involved in the process of muscle regeneration are observed to be up-regulated in SJL mice, including cardiac ankyrin repeated protein (CARP), Neuraminidase 2, interleukin-6, insulin-like growth factor-2 and osteopontin. We found the upregulation of S100 calcium binding proteins, neural precursor cell expressed, developmentally down-regulated gene 4-like (NEDD4L) with C2 domain, and intracellular protein traffic associated proteins (Rab6 and Rab2). These proteins have the potential to interact with dysferlin. We must reveal some other molecules which may work with dysferlin in order to clarify the pathological network of dysferlinopathy. This process may lead to future improvements in the therapy for human dysferlinopathy.