All non-sensory pertussis toxin sensitive G protein alpha subunits have been knocked out in earlier years by gene targeting. Previously we had found that Gi2 KO mice develop ulcerative colitis (UC) in 129Sv mice but not C57BL mice, and that Go KO mice develop a turning syndrome. In collaborative studies we also noted that expression of Go-alpha blocks cAMP-induced neurite outgrowth. During the previous year we had discovered that Gi2 KO mice have a defect in cerebellar foliation, that the Gi2-alpha subunit has an intrinsic cardioprotective effect (in collaboration with Stefan Herzig), and that it plays a role in B cell development leading to a decrease in T2 transitional B cells as well as B-1a B cells. During this last year w found that Gi2 is required for the protective effect that B cells have against T cell induced colitis (in collaboration with Jonathan Braun at UCLA), that ulcerative colitis in 129Sv mice lacking Gi2-alpha is induced by an unknown pathogen to which the 129Sv mice are susceptible but C57Black mice are not, and that Go-alpha interacting with PKA in the cytosol interferes with nuclear effects of cAMP by retaining PKA in the cytosol (in collaboration with Heayoung Suh-Kim). A vector has been made to generate transgenic mice that express Go-alpha only in dopaminergic neurons to test the hypothesis that Go-deficient mice circle because of lack of Go in their dopaminergic neurons. HIT and RUN (also IN and OUT) vectors were designed and genetically engineered mice have been obtained with loxP sites flanking either Gi2 alpha exons 2-3-4 or Go exon exon 6.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES101643-03
Application #
7174359
Study Section
(LST)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Marshall, John; Zhou, Xiao-Zhong; Chen, Gang et al. (2018) Antidepression action of BDNF requires and is mimicked by G?i1/3 expression in the hippocampus. Proc Natl Acad Sci U S A 115:E3549-E3558
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