Abstract
Mice with genomic knockout of either melanocortin type 3 receptors (MC3R-/-), type 4 receptors (MC4R-/-) or knockout of both (double knockout, DKO) were tested for their anorectic response to the mixed MC3/4R agonist, MTII, injected into the anterior cerebral ventricle. Wild type (WT) mice showed a strong anorexia and, as expected, DKO were completely unresponsive to MTII. In contrast, both MC3R-/- and MC4R-/- showed a partial anorectic response. Induction of c-Fos immunoreactivity by MTII was examined in brain regions including paraventricular hypothalamus (PVN) and area postrema (AP). Compared with WT, MC4R-/- showed no activation in AP but showed normal activation in PVN, whereas MC3R-/- showed reduced activation in PVN but not in AP. RT-PCR analysis showed that hypothalamic mRNA for MC3R in MC4R-/- and for MC4R in MC3R-/- was unaltered from WT levels. These data suggest that both receptor subtypes are involved in the behavioral action of MTII, and that the critical receptors are in different brain regions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2314-2317 |
| Number of pages | 4 |
| Journal | Peptides |
| Volume | 31 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2010 |
Bibliographical note
Funding Information:This work was funded in part by NIH grants RO1DK064712 and RO1DK057080 . We thank Dr. Dennis Huszar and Millennium Pharmaceuticals/Genelogic for providing the breeding stock MC4R−/− mice, Dr. Lex VanDerPloeg and Merck Research for providing the breeding stock MC3R−/− mice, and both David White at Genelogic and Merck Research for allowing us to generate and study the MC3R−/− × MC4R−/− double knockout mice.