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United States Department of Agriculture

Agricultural Research Service

Research Project: BONE METABOLISM IN OBESITY Title: Mx1-cre mediated Rgs12 conditional knockout mice exhibit increased bone mass phenotype

Authors
item Yang, Shuyiang -
item Li, Yi-Ping -
item Liu, Tongjun -
item He, Xianoing -
item Yuan, Xue -
item Li, Chunyi -
item Cao, Jay
item Kim, Yunjung -

Submitted to: Genesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 6, 2013
Publication Date: March 1, 2013
Repository URL: http://handle.nal.usda.gov/10113/58059
Citation: Yang, S., Li, Y., Liu, T., He, X., Yuan, X., Li, C., Cao, J.J., Kim, Y. 2013. Mx1-cre mediated Rgs12 conditional knockout mice exhibit increased bone mass phenotype. Genesis. 51:201-209.

Interpretive Summary: Regulators of G-protein Signaling (RGS proteins) play an important role in physiology and human diseases. RGS12, the largest protein of the RGS protein family, plays a critical role in regulating calcium signaling, cell differentiation and migration in vitro. We successfully generated RGS12 conditional mutant mice. Mice homozygous for RGS12floxneo/floxneo and RGS12flox/flox alleles are normal and fertile. By using inducible Mx1-cre and inducibly deleting RGS12 at late embryonic stage (E14.5 – E18.5), we found that RGS12 mutant mice showed apparent growth retardation with osteopetrosis phenotype, abnormal submandibular gland morphology and resistance of LPS mediated bone loss. Thus, RGS12flox/flox conditional mice provide a valuable tool for systematic tissue-specific function analysis of RGS12 in embryonic and postnatal development and diseases.

Technical Abstract: Regulators of G-protein Signaling (Rgs) proteins are the members of a multigene family of GTPase-accelerating proteins (GAP) for the Galpha subunit of heterotrimeric G-proteins. Rgs proteins play critical roles in the regulation of G protein couple receptor (GPCR) signaling in normal physiology and human diseases such as cancer, heart diseases, and inflammation. Rgs12 is the largest protein of the Rgs protein family. Some in vitro studies have demonstrated that Rgs12 plays a critical role in regulating cell differentiation and migration; however its function and mechanism in vivo is largely unknown. Here, we generated a floxed Rgs12 allele (Rgs12(flox/flox) ) in which the exon 2, containing both PDZ and PTB_PID domains of Rgs12, was flanked with two loxp sites. By using the inducible Mx1-cre and Poly I:C system to specifically delete Rgs12 at postnatal 10 days in interferon-responsive cells including monocyte and macrophage cells, we found that Rgs12 mutant mice had growth retardation with the phenotype of increased bone mass. We further found that deletion of Rgs12 reduced osteoclast numbers and had no significant effect on osteoblast formation. Thus,Rgs12(flox/flox) conditional mice provide a valuable tool for in vivo analysis of Rgs12 function and mechanism through time- and cell-specific deletion of Rgs12.

Last Modified: 8/22/2014
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