Agouti signaling protein stimulates cell division in "viable yellow" (A(vy)/a) mouse liver.
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.
Wolff
George L
GL
Arkansas Children's Nutrition Center, Little Rock, AR72202, USA.
Stanley
J Steven
JS
Ferguson
Matthew E
ME
Simpson
Pippa M
PM
Ronis
Martin J J
MJ
Badger
Thomas M
TM
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
D054366:Agouti Signaling Protein; D018809:Proliferating Cell Nuclear Antigen