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ORIGINAL RESEARCH ARTICLE

A BRIEF COMMUNICATION

Agouti Signaling Protein Stimulates Cell Division in "Viable Yellow" (A^vy/a) Mouse Liver

George L. Wolff^*,1, J. Steven Stanley^*, Matthew E. Ferguson^*, Pippa M. Simpson, Martin J. J. Ronis^*, and Thomas M. Badger^*,,,1

^* Arkansas Children’s Nutrition Center; Department of Pediatrics; Department of Pharmacology/Toxicology; and Department of Physiology/Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202

To whom requests for reprints should be addressed at ¹ 2802 Millbrook Road, Little Rock, AR 72227-3038. E-mail: gwolffar{at}prodigy.net (G.L.W.), or Children’s Nutrition Center, 1120 Marshall Street, Little Rock, AR 72202. E-mail; badgerthomasm{at}uams.edu (T.M.B.)

Enhanced linear growth, hyperplasia, and tumorigenesis are well-known characteristics of "viable yellow" agouti A^vy/- mice (Wolff GL, Roberts DW, Mountjoy KG. Physiol Genomics 1:151–163, 1999); 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 A^vy/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 reverse transcriptase polymerase chain reaction assays were performed on liver samples from mottled yellow A^vy/a, pseudoagouti A^vy/a, and black a/a VY mice to determine mitotic indices and expression levels of A^vy and a in relation to the expression level of the housekeeping gene hprt. We found that ASIP levels were ~100-fold higher in yellow than in pseudoagouti or black mice and that the proportion of PCNA-positive hepatocytes was greater (P < 0.001) in yellow than in pseudoagouti or black mice.

Key Words: agouti signaling protein • cell division • pseudoagouti mice