Location: Children's Nutrition Research CenterTitle: Characterization of PICOT-deficient mice) Author
Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: 11/8/2007
Publication Date: 1/27/2008
Citation: Cheng, N. 2008. Characterization of PICOT-deficient mice [abstract]. 2008 Keystone Symposia. January 22-27, 2008, Breckinridge, Colorado p. 67. Interpretive Summary:
Technical Abstract: Oxidative stress impairs cell growth, differentiation, proliferation, and immune system. It has been demonstrated that oxidative damage is strongly associated with all-cause chronic diseases and metabolic disorders, such as obesity and diabetes. Regulation of redox-state is thought to play a critical role in protecting cells against oxidative damage. PICOT (protein kinase C interacting cousin of thioredoxin) is a newly identified class of glutaredoxins (Grxs), monothiol Grxs, which are conserved in both prokaryotes and eukaryotes. Previous studies demonstrated that PICOTs from mammalian cells, yeast, and plants play an important role in regulating cellular redox signaling. In the human genome, there are two monothiol Grxs identified and closer to yeast Grx 3-5. The biological function of this novel HsPICOT has not been fully characterized. Gene expression analysis revealed that HsPICOT was ubiquitously expressed in all tissues and organs with high accumulation of RNA transcripts in heart, spleen, fat tissues, and reproductive organs. It appears that HsPICOT-GFP fusion was evenly distributed in the cytosol when expressed in HEK293 cells. In the yeast heterologous expression assay, HsPICOT was able to complement yeast grx3/4 mutant phenotypes, suggesting a conserved function among this group of proteins. In order to further delineate the function of HsPICOT in vivo, PICOT-deficient mice have been generated. Genetic analysis indicated that HsPICOT was required for early embryonic growth and development. In PICOT+/-mice, both RNA and protein levels were drastically reduced. Characterization of HsPICOT function and biochemical and physiological analyses of those heterozygotes will be presented.