The mahogany protein is a receptor involved in suppression of obesity
| Autor: | Chris Ebeling, Elizabeth A. Woolf, Dennis Huszar, Deborah L. Nagle, Sonja H. McGrail, Karen J. Moore, Barry J. Dussault, Paul Burn, Victoria Fairchild-Huntress, George A. Carlson, Peer Bork, Lisa DiRocco, Pei Ge, Jill Montagno, James Vitale, Lisa Holmgren, Linda Baldini, Julie Gilchrist, John Keilty |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Positional cloning Protein Conformation Molecular Sequence Data Locus (genetics) Mice Gene mapping Gene expression Animals Humans Amino Acid Sequence Obesity Cloning Molecular Receptor Gene Caenorhabditis elegans Genetics Mice Inbred C3H Multidisciplinary biology Membrane Proteins biology.organism_classification Physical Chromosome Mapping Phenotype Diet Female |
| Zdroj: | Nature. 398(6723) |
| ISSN: | 0028-0836 |
| Popis: | Genetic studies have shown that mutations within the mahogany locus suppress the pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant. Here we identify the mahogany gene and its product; this study, to our knowledge, represents the first positional cloning of a suppressor gene in the mouse. Expression of the mahogany gene is broad; however, in situ hybridization analysis emphasizes the importance of its expression in the ventromedial hypothalamic nucleus, a region that is intimately involved in the regulation of body weight and feeding. We present new genetic studies that indicate that the mahogany locus does not suppress the obese phenotype of the melanocortin-4-receptor null allele or those of the monogenic obese models (Lep(db), tub and Cpe(fat)). However, mahogany can suppress diet-induced obesity, the mechanism of which is likely to have implications for therapeutic intervention in common human obesity. The amino-acid sequence of the mahogany protein suggests that it is a large, single-transmembrane-domain receptor-like molecule, with a short cytoplasmic tail containing a site that is conserved between Caenorhabditis elegans and mammals. We propose two potential, alternative modes of action for mahogany: one draws parallels with the mechanism of action of low-affinity proteoglycan receptors such as fibroblast growth factor and transforming growth factor-beta, and the other suggests that mahogany itself is a signalling receptor. |
| Databáze: | OpenAIRE |
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