Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2007
Publication Date: 11/1/2007
Citation: Wolff, G.L., Stanley, S.J., Ferguson, M.E., Simpson, P.M., Ronis, M.J., Badger, T.M. 2007. Agouti signaling protein stimulates cell division in "viable yellow" (A vy/a) mouse liver. Experimental Biology and Medicine. 232(10):1326-1329.
Interpretive Summary: The agouti mouse produces an excess of a protein known as the agouti signaling protein (ASIP). Mice with high levels of this protein are obese, and mice with low amounts of this protein are lean. We have been studying this mouse to learn more about obesity. In this paper, we describe that one major effect of ASIP is to stimulate cell division, and this may be an important mechanism by which these animals become obese. Such studies may lead to interventions to help prevent or reverse obesity in people.
Technical Abstract: Enhanced linear growth, hyperplasia, and tumorigenesis are well-known characteristics of "viable yellow" agouti Avy/- mice (1); however, the functional basis for this aspect of the phenotype is unknown. In the present study, we ascertained whether agouti signaling protein (ASIP) levels in Avy/a or a/a livers are associated with hepatocyte proliferation as a possible factor in promotion of hepatocellular tumor formation. Proliferating Cell Nuclear Antigen (PCNA) assays and quantitative real-time RT-PCR assays were performed on liver samples from mottled yellow Avy/a, pseudoagouti Avy/a, and black a/a VY mice to determine mitotic indices and expression levels of Avy and a relative to the expression level of the housekeeping gene hprt. We found that ASIP levels were about 100-fold higher in yellow than in pseudoagouti or black mice and that the proportion of PCNA-positive hepatocytes was greater (P<.001) in yellow than in pseudoagouti or black mice.