PMID- 10086355
OWN - NLM
STAT- MEDLINE
DCOM- 19990329
LR  - 20061115
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 398
IP  - 6723
DP  - 1999 Mar 11
TI  - The mahogany protein is a receptor involved in suppression of obesity.
PG  - 148-52
AB  - 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.
FAU - Nagle, D L
AU  - Nagle DL
AD  - Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
FAU - McGrail, S H
AU  - McGrail SH
FAU - Vitale, J
AU  - Vitale J
FAU - Woolf, E A
AU  - Woolf EA
FAU - Dussault, B J Jr
AU  - Dussault BJ Jr
FAU - DiRocco, L
AU  - DiRocco L
FAU - Holmgren, L
AU  - Holmgren L
FAU - Montagno, J
AU  - Montagno J
FAU - Bork, P
AU  - Bork P
FAU - Huszar, D
AU  - Huszar D
FAU - Fairchild-Huntress, V
AU  - Fairchild-Huntress V
FAU - Ge, P
AU  - Ge P
FAU - Keilty, J
AU  - Keilty J
FAU - Ebeling, C
AU  - Ebeling C
FAU - Baldini, L
AU  - Baldini L
FAU - Gilchrist, J
AU  - Gilchrist J
FAU - Burn, P
AU  - Burn P
FAU - Carlson, G A
AU  - Carlson GA
FAU - Moore, K J
AU  - Moore KJ
LA  - eng
SI  - GENBANK/AF116897
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (ATRN protein, human)
RN  - 0 (Atrn protein, mouse)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cloning, Molecular
MH  - Diet
MH  - Female
MH  - Humans
MH  - Male
MH  - Membrane Proteins/chemistry/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Molecular Sequence Data
MH  - Obesity/*genetics
MH  - Physical Chromosome Mapping
MH  - Protein Conformation
EDAT- 1999/03/23 03:03
MHDA- 2001/03/23 10:01
CRDT- 1999/03/23 03:03
PHST- 1999/03/23 03:03 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/23 03:03 [entrez]
AID - 10.1038/18210 [doi]
PST - ppublish
SO  - Nature. 1999 Mar 11;398(6723):148-52. doi: 10.1038/18210.