These Mc3r-/- mutant mice possess a floxed STOP-neo cassette upstream of the start codon, and an IRES-GFP cassette downstream of the stop codon of the melanocortin 3 receptor (Mc3r) gene. MC3R is a G-protein coupled receptor for the melanocyte-stimulating hormone. It is expressed in the hypothalamic and limbic regions of the brain and in some peripheral tissues including the renal cortex and medulla, and the immune system. MC3R contributes to the regulation of body composition, salt excretion, immune function, and energy homeostasis. Homozygous MC3R-/- males are fertile while homozygous females are poor breeders. These floxed-STOP mice exhibit increased susceptibility to diet-induced obesity, with increased fat mass and decreased lean mass when fed a standard chow diet. These mice can also exhibit increased circulating insulin and leptin levels, changes in serum triglyceride levels, changes in the respiratory exchange ratio (indicating altered whole body substrate preference), and decreased physical activity.
When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have the STOP cassette deleted, allowing MC3R expression in cre-expressing tissues.
For example, when bred to B6.Cg-Tg(Nes-cre)1Kln/J (Stock No. 003771) expressing Cre in the nervous system, the resulting offspring display a partial rescue of the obesity phenotype.
When bred to FVB-Tg(Nr5a1-cre)2Lowl/J (Stock No. 006364) expressing Cre in steroidogenic factor-1 (SF1)-positive neurons, the resulting offspring exhibit improvements in metabolic homeostasis.
The donating investigator reports that although an
IRES-GFP is present in the allele, expression is too low to detect.
