Pleiotropic phenotype of a genomic knock-in of an RGS-insensitive G184S Gnai2 allele

Xinyan Huang, Ying Fu, Raelene A. Charbeneau, Thomas L. Saunders, Douglas K. Taylor, Kurt D. Hankenson, Mark W. Russell, Louis G. D'Alecy, Richard R. Neubig

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Signal transduction via guanine nucleotide binding proteins (G proteins) is involved in cardiovascular, neural, endocrine, and immune cell function. Regulators of G protein signaling (RGS proteins) speed the turn-off of G protein signals and inhibit signal transduction, but the in vivo roles of RGS proteins remain poorly defined. To overcome the redundancy of RGS functions and reveal the total contribution of RGS regulation at the Gαi2 subunit, we prepared a genomic knock-in of the RGS-insensitive G184S Gnai2 allele. The Gαi2G184S knock-in mice show a dramatic and complex phenotype affecting multiple organ systems (heart, myeloid, skeletal, and central nervous system). Both homozygotes and heterozygotes demonstrate reduced viability and decreased body weight. Other phenotypes include shortened long bones, a markedly enlarged spleen, elevated neutrophil counts, an enlarged heart, and behavioral hyperactivity. Heterozygous Gα12 +/G184S mice show some but not all of these abnormalities. Thus, loss of RGS actions at Gα12 produces a dramatic and pleiotropic phenotype which is more evident than the phenotype seen for individual RGS protein knockouts.

Original languageEnglish (US)
Pages (from-to)6870-6879
Number of pages10
JournalMolecular and Cellular Biology
Volume26
Issue number18
DOIs
StatePublished - Sep 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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