Biochemical and Biophysical Research Communications
G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice
Section snippets
Materials and methods
Generation and maintenance of the GPCR12 knockout mice. Heterozygous GPCR12 knockout mice (GPCR+/−) were obtained from Deltagen (San Carlos, CA, USA). A schematic diagram of the mouse GPCR12 gene, including the disrupted region, is outlined in Fig. 1. The GPCR12 gene was targeted by homologous recombination in ES cells derived from 129/OlaHsd mouse substrain and injected into blastocysts. Mice carrying a disrupted GPCR12 gene were generated by breeding the chimeric mice with C57BL/6 females.
Generation of the GPCR12 KO mice
GPCR12 KO mice were generated by targeted deletion of a 353-bp segment of the coding region in exon 2 (Fig. 1). This region corresponds to nucleotides 155–507 of the mRNA. Genotyping of chimeric mice and subsequent progeny was performed by PCR and confirmed by Southern blot analysis (data not shown). The genomic region deleted by the targeting vector was replaced by a Lac Z-Neo reporter cassette that could be used to analyse GPCR12 expression in vivo. The ratio of offspring genotypes did not
Discussion
In this study, mice having a disruption in the G protein-coupled receptor 12 gene (GPCR12 KO) were studied to investigate the importance of GPCR12 in metabolism. This is the first study of this mouse line reported in the literature. We found that GPCR12 deficiency resulted in obesity and dyslipidemia. The increased body weight and obesity may be explained by a decrease in energy expenditure since GPCR12 KO mice had unaltered food intake, locomotor activity, body temperature, and faeces energy
Acknowledgments
Lena Amrot Fors, Anna Tuneld, Charlotte Lindgren, Anne-Cristine Carlsson, Martina Johansson, Gisela Häggblad, and Marie-Louise Berglund Zackrisson who kindly helped with the serum assays. Also, we thank Magnus Kjaer for invaluable help with statistical analysis.
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Both authors have contributed equally to this work placed by alphabetical order.