Dataset Information

Identification of mutations through dominant screening for obesity using C57BL/6 substrains.

ABSTRACT: The discovery of leptin substantiated the usefulness of a forward genetic approach in elucidating the molecular network regulating energy metabolism. However, no successful dominant screening for obesity has been reported, which may be due to the influence of quantitative trait loci between the screening and counter strains and the low fertility of obese mice. Here, we performed a dominant screening for obesity using C57BL/6 substrains, C57BL/6J and C57BL/6N, with the routine use of in vitro fertilization. The screening of more than 5000 mutagenized mice established two obese pedigrees in which single nucleotide substitutions in Mc4r and Sim1 genes were identified through whole-exome sequencing. The mutation in the Mc4r gene produces a premature stop codon, and the mutant SIM1 protein lacks transcriptional activity, showing that the haploinsufficiency of SIM1 and MC4R results in obesity. We further examined the hypothalamic neuropeptide expressions in the mutant pedigrees and mice with diet-induced obesity, which showed that each obesity mouse model has distinct neuropeptide expression profiles. This forward genetic screening scheme is useful and applicable to any research field in which mouse models work.

SUBMITTER: Hossain MS

PROVIDER: S-EPMC5009433 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Identification of mutations through dominant screening for obesity using C57BL/6 substrains.

Hossain Mohammad Sarowar MS Asano Fuyuki F Fujiyama Tomoyuki T Miyoshi Chika C Sato Makito M Ikkyu Aya A Kanno Satomi S Hotta Noriko N Kakizaki Miyo M Honda Takato T Kim Staci J SJ Komiya Haruna H Miura Ikuo I Suzuki Tomohiro T Kobayashi Kimio K Kaneda Hideki H Kumar Vivek V Takahashi Joseph S JS Wakana Shigeharu S Funato Hiromasa H Yanagisawa Masashi M

Scientific reports 20160902

The discovery of leptin substantiated the usefulness of a forward genetic approach in elucidating the molecular network regulating energy metabolism. However, no successful dominant screening for obesity has been reported, which may be due to the influence of quantitative trait loci between the screening and counter strains and the low fertility of obese mice. Here, we performed a dominant screening for obesity using C57BL/6 substrains, C57BL/6J and C57BL/6N, with the routine use of in vitro fer ...[more]

PMID: 27585985

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Dataset Information

Identification of mutations through dominant screening for obesity using C57BL/6 substrains.

Publications

Identification of mutations through dominant screening for obesity using C57BL/6 substrains.

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