title: Agouti signaling protein stimulates cell division in "viable yellow" (A(vy)/a) mouse liver.
abstract: 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 approximately 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.
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, AR72202, USA.
authors.forename: George L
authors.initials: GL
authors.lastname: Wolff
authors.forename: J Steven
authors.initials: JS
authors.lastname: Stanley
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Ferguson
authors.forename: Pippa M
authors.initials: PM
authors.lastname: Simpson
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology; D008099:Liver / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054366:Agouti Signaling Protein; D018809:Proliferating Cell Nuclear Antigen