Severe obesity and insulin resistance due to deletion of the maternal Gsalpha allele is reversed by paternal deletion of the Gsalpha imprint control region.

Endocrinology
Tao XieLee S Weinstein

Abstract

The G protein alpha-subunit G(s)alpha mediates receptor-stimulated cAMP production and is imprinted with reduced expression from the paternal allele in specific tissues. Disruption of the G(s)alpha maternal (but not paternal) allele leads to severe obesity, hypertriglyceridemia, and insulin resistance in mice and obesity in patients with Albright hereditary osteodystrophy. Paternal deletion of a G(s)alpha imprint control region (1A) leads to loss of tissue-specific G(s)alpha imprinting. To determine whether the metabolic abnormalities resulting from disruption of the G(s)alpha maternal allele could be reversed by loss of paternal G(s)alpha imprinting, females with a heterozygous G(s)alpha exon 1 deletion were mated to males with heterozygous deletion of the imprint control region (1A) to generate mice with maternal G(s)alpha deletion (E1(m-)), paternal 1A deletion (1A(p-)), double mutants (E1(m-):1A(p-)), and wild type. E1(m-) mice developed obesity, glucose intolerance, insulin resistance, and hypertriglyceridemia, which were all normalized by the paternal 1A deletion in E1(m-):1A(p-) mice. Obesity in E1(m-) was associated with reduced energy expenditure and sympathetic nerve activity, and these were also normalized in E1(m-):...Continue Reading

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Citations

Jan 7, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Heather A LawsonJames M Cheverud
Jul 11, 2013·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Sally A EatonJo Peters
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Apr 28, 2010·Molecular and Cellular Biology·Chelsea M BrideauPaul D Soloway
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Jan 7, 2011·European Journal of Pharmacology·Min ChenLee S Weinstein
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May 6, 2017·Frontiers in Genetics·Helle Krogh PedersenSøren Brunak

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