| First Author | Vicent D | Year | 1998 |
| Journal | Diabetes | Volume | 47 |
| Issue | 9 | Pages | 1451-8 |
| PubMed ID | 9726234 | Mgi Jnum | J:49410 |
| Mgi Id | MGI:1277455 | Doi | 10.2337/diabetes.47.9.1451 |
| Citation | Vicent D, et al. (1998) Alterations in skeletal muscle gene expression of ob/ob mice by mRNA differential display [published erratum appears in Diabetes 1998 Dec;47(12):1978]. Diabetes 47(9):1451-8 |
| abstractText | To identify molecules that contribute to insulin resistance, we compared the patterns of gene expression in skeletal muscle of the obese ob/ob mouse, a genetic model of obesity and severe insulin resistance, with that of its thin littermate (ob/+) using the mRNA differential display method. From about 9,000 cDNAs displayed, we found 12 differentially expressed in ob/ob mice skeletal muscle that could be recovered from the differential display gels and confirmed by Northern blot analysis and sequenced. Eight mRNAs were overexpressed in ob/ob muscle: Id2 (a negative regulator of the basic helix-loop-helix family of transcription factors), fast skeletal muscle troponin T, ribosomal protein L3, the integral protein of the peroxisomal membrane 22PMP, the mammalian homolog of geranyl-geranyl pyrophosphate synthase, an mRNA related to phosphatidylinositol-glycan-specific phospho-lipase D, and two unknown mRNAs. The level of overexpression of these mRNAs in skeletal muscle varied from a 500% increase to as little as a 25% increase. Two mRNAs were under- expressed 20-35%, including the f-subunit of mitochondrial ATP synthase and a retrovirus-related DNA. Two proteins with multiple transcripts, skeletal muscle alpha-tropomyosin and one for a repetitive sequence, showed a change in mRNA pattern of expression in the muscle of the ob/ob mouse. Because the primary genetic defect in the ob/ob mouse is known to be in the leptin gene, these data indicate how acquired alterations in gene expression of multiple classes of proteins may play a role in the complex pathogenesis of insulin resistance in obesity and diabetes. |
