RGD Reference Report - Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. - Rat Genome Database

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Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean.

Authors: Yamada, M  Miyakawa, T  Duttaroy, A  Yamanaka, A  Moriguchi, T  Makita, R  Ogawa, M  Chou, CJ  Xia, B  Crawley, JN  Felder, CC  Deng, CX  Wess, J 
Citation: Yamada M, etal., Nature 2001 Mar 8;410(6825):207-12.
RGD ID: 734983
Pubmed: PMID:11242080   (View Abstract at PubMed)
DOI: DOI:10.1038/35065604   (Journal Full-text)

Members of the muscarinic acetylcholine receptor family (M1-M5) have central roles in the regulation of many fundamental physiological functions. Identifying the specific receptor subtype(s) that mediate the diverse muscarinic actions of acetylcholine is of considerable therapeutic interest, but has proved difficult primarily because of a lack of subtype-selective ligands. Here we show that mice deficient in the M3 muscarinic receptor (M3R-/- mice) display a significant decrease in food intake, reduced body weight and peripheral fat deposits, and very low levels of serum leptin and insulin. Paradoxically, hypothalamic messenger RNA levels of melanin-concentrating hormone (MCH), which are normally upregulated in fasted animals leading to an increase in food intake, are significantly reduced in M3R-/- mice. Intra-cerebroventricular injection studies show that an agouti-related peptide analogue lacked orexigenic (appetite-stimulating) activity in M3R-/- mice. However, M3R-/- mice remained responsive to the orexigenic effects of MCH. Our data indicate that there may be a cholinergic pathway that involves M3-receptor-mediated facilitation of food intake at a site downstream of the hypothalamic leptin/melanocortin system and upstream of the MCH system.

Objects referenced in this article
Gene CHRM3 cholinergic receptor muscarinic 3 Homo sapiens
Gene Chrm3 cholinergic receptor, muscarinic 3, cardiac Mus musculus
Gene Chrm3 cholinergic receptor, muscarinic 3 Rattus norvegicus

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