The mahogany protein is a receptor involved in suppression of obesity

Deborah L. Nagle, Sonja H. McGrail, James Vitale, Elizabeth A. Woolf, Barry J. Dussault, Lisa DiRocco, Lisa Holmgren, Jill Montagno, Peer Bork, Dennis Huszar, Victoria Fairchild-Huntress, Pei Ge, John Keilty, Chris Ebeling, Linda Baldini, Julie Gilchrist, Paul Burn, George A. Carlson and Karen J. Moore ()
Additional contact information
Deborah L. Nagle: Millennium Pharmaceuticals, Inc.
Sonja H. McGrail: Millennium Pharmaceuticals, Inc.
James Vitale: Millennium Pharmaceuticals, Inc.
Elizabeth A. Woolf: Millennium Pharmaceuticals, Inc.
Barry J. Dussault: Millennium Pharmaceuticals, Inc.
Lisa DiRocco: Millennium Pharmaceuticals, Inc.
Lisa Holmgren: Millennium Pharmaceuticals, Inc.
Jill Montagno: Millennium Pharmaceuticals, Inc.
Peer Bork: European Molecular Biology Laboratories
Dennis Huszar: Millennium Pharmaceuticals, Inc.
Victoria Fairchild-Huntress: Millennium Pharmaceuticals, Inc.
Pei Ge: Millennium Pharmaceuticals, Inc.
John Keilty: Millennium Pharmaceuticals, Inc.
Chris Ebeling: McLaughlin Research Institute for Biomedical Sciences
Linda Baldini: McLaughlin Research Institute for Biomedical Sciences
Julie Gilchrist: McLaughlin Research Institute for Biomedical Sciences
Paul Burn: Hoffman-La Roche, Inc.
George A. Carlson: McLaughlin Research Institute for Biomedical Sciences
Karen J. Moore: Millennium Pharmaceuticals, Inc.

Nature, 1999, vol. 398, issue 6723, 148-152

Abstract: Abstract Genetic studies have shown that mutations within the mahogany locus1 suppress the pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant2,3. 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 allele4 or those of the monogenic obese models (Lepdb, tub and Cpefat). 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-β, and the other suggests that mahogany itself is a signalling receptor.

Date: 1999
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/18210 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:398:y:1999:i:6723:d:10.1038_18210

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/18210

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().