• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Alternative Gnas gene products have opposite effects on glucose and lipid metabolism.

Gnas is an imprinted gene with multiple gene products resulting from alternative splicing of different first exons onto a common exon 2. These products include stimulatory G protein alpha-subunit (G(s)alpha), the G protein required for receptor-stimulated cAMP production; extralarge G(s)alpha (XLalphas), a paternally expressed G(s)alpha isoform; and neuroendocrine-specific protein (NESP55), a maternally expressed chromogranin-like protein. G(s)alpha undergoes tissue-specific imprinting, being expressed primarily from the maternal allele in certain tissues. Heterozygous mutation of exon 2 on the maternal (E2m-/+) or paternal (E2+/p-) allele results in opposite effects on energy metabolism. E2m-/+ mice are obese and hypometabolic, whereas E2+/p- mice are lean and hypermetabolic. We now studied the effects of G(s)alpha deficiency without disrupting other Gnas gene products by deleting G(s)alpha exon 1 (E1). E1+/p- mice lacked the E2+/p- phenotype and developed obesity and insulin resistance. The lean, hypermetabolic, and insulin-sensitive E2+/p- phenotype appears to result from XLalphas deficiency, whereas loss of paternal-specific G(s)alpha expression in E1+/p- mice leads to an opposite metabolic phenotype. Thus, alternative Gnas gene products have opposing effects on glucose and lipid metabolism. Like E2m-/+ mice, E1m-/+ mice had s.c. edema at birth, presumably due to loss of maternal G(s)alpha expression. However, E1m-/+ mice differed from E2m-/+ mice in other respects, raising the possibility for the presence of other maternal-specific gene products. E1m-/+ mice had more severe obesity and insulin resistance and lower metabolic rate relative to E1+/p- mice. Differences between E1m-/+ and E1+/p- mice presumably result from differential effects on G(s)alpha expression in tissues where G(s)alpha is normally imprinted.

Pubmed ID: 15883378

Authors

  • Chen M
  • Gavrilova O
  • Liu J
  • Xie T
  • Deng C
  • Nguyen AT
  • Nackers LM
  • Lorenzo J
  • Shen L
  • Weinstein LS

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

May 17, 2005

Associated Grants

None

Mesh Terms

  • Alternative Splicing
  • Analysis of Variance
  • Animals
  • Blood Glucose
  • Blotting, Northern
  • Body Composition
  • DNA Primers
  • Energy Metabolism
  • GTP-Binding Protein alpha Subunits, Gs
  • Genetic Vectors
  • Genomic Imprinting
  • Glucose
  • Insulin Resistance
  • Lipid Metabolism
  • Mice
  • Mice, Knockout
  • Mutation
  • Phenotype
  • Protein Isoforms
  • Radioimmunoassay
  • Triglycerides