FIGURE 1.

Gene targeting strategy and assessment of the obese phenotype of Mc3rTB/TB mice (data in this and subsequent figures are presented as mean ± S.E.). A, schematic showing insertion of the LoxP-flanked transcriptional blocker (LoxTB) into the mouse Mc3r gene. An IRES-acGFP cassette inserted 3′ of the MC3R open reading frame (ORF) is not shown. B, analysis of hypothalamic Mc3r expression by in situ hybridization in Mc3r^Δ/Δ, Mc3r^TB/TB, and SF1-Cre;Mc3r^TB/TB mice. Mc3r expression is observed in the VMH and arcuate nucleus of the hypothalamus (ARC) of Mc3r^Δ/Δ mice, but not in Mc3r^TB/TB mice. SF1-Cre;Mc3r^TB/TB mice exhibit diffuse signal in the VMH but not in the arcuate nucleus of the hypothalamus. 3V, third ventricle. C–D, body weight and analysis of fat-free mass and fat mass in female and male WT and Mc3r^TB/TB mice aged 8–10 weeks (n = 6–11/group). Mc3r^TB/TB mice had normal body weight but exhibited reduced FFM and increased FM. *, p < 0.05 versus WT. E, accelerated DIO in female Mc3r^TB/TB mice. Mice were fed a purified low fat diet (LFD, 10% kJ/fat) or HFD (60% kJ/fat) for 6 weeks. Body weight (left panel) was significantly affected by genotype in the HFD-fed group but not in mice fed low fat diet. The right panel shows body composition. The difference in body weight after HFD feeding was due to increased FM. *, p < 0.05 versus WT.