Metabolic parameters and emotionality are little affected in G-protein coupled receptor 12 (Gpr12) mutant mice

Abstract

Background: G-protein coupled receptors (GPR) bear the potential to serve as yet unidentified drug targets for psychiatric and metabolic disorders. GPR12 is of major interest given its putative role in metabolic function and its unique brain distribution, which suggests a role in emotionality and affect. We tested Gpr12 deficient mice in a series of metabolic and behavioural tests and subjected them to a well-established high-fat diet feeding protocol.

Methodology/principal findings: Comparing the mutant mice with wild type littermates, no significant differences were seen in body weight, fatness or weight gain induced by a high-fat diet. The Gpr12 mutant mice displayed a modest but significant lowering of energy expenditure and a trend to lower food intake on a chow diet, but no other metabolic parameters, including respiratory rate, were altered. No emotionality-related behaviours (assessed by light-dark box, tail suspension, and open field tests) were affected by the Gpr12 gene mutation.

Conclusions/significance: Studying metabolic and emotionality parameters in Gpr12 mutant mice did not reveal a major phenotypic impact of the gene mutation. Compared to previous results showing a metabolic phenotype in Gpr12 mice with a mixed 129 and C57Bl6 background, we suggest that a more pure C57Bl/6 background due to further backcrossing might have reduced the phenotypic penetrance.

Figure 1. Body weight gain on lab chow.

Body weight development in Gpr12 knockout (KO; n = 8) mice (red line) and wildtype (WT; n = 8) mice (dotted line) showed no difference at any measured time point.

Figure 2. Energy expenditure.

(A) Relative energy expenditure (EE), (B) respiratory exchange rate (RER) and (C) relative food intake (FI) of Gpr12 knockout (KO; n = 8) mice (red line) and wildtype (WT; n = 8) mice (dotted line). Whereas EE was significantly different between Gor12 KO and WT, RER and FI did not differ (2-way ANOVA with factors time and genotype; **p<0.01).

Figure 3. Body weight gain on high-fat diet.

Body weight development in Gpr12 knockout (KO; n = 8) mice (red line) and wildtype (WT; n = 8) mice (dotted line) fed with lab chow, high-fat diet or after fasting showed no difference at any measured time point.