A transgenic mouse assay for agouti protein activity.
The mouse agouti gene encodes an 131 amino acid paracrine signaling molecule that instructs hair follicle melanocytes to switch from making black to yellow pigment. Expression of agouti during the middle part of the hair growth cycle in wild-type mice produces a yellow band on an otherwise black hair. The ubiquitous unregulated expression of agouti in mice carrying dominant yellow alleles is associated with pleiotropic effects including increased yellow pigment in the coat, obesity, diabetes and increased tumor susceptibility. Agouti shows no significant homology to known genes, and the molecular analysis of agouti alleles has shed little new light on the important functional elements of the agouti protein. In this paper, we show that agouti expression driven by the human beta-ACTIN promoter produces obese yellow transgenic mice and that this can be used as an assay for agouti activity. We used this assay to evaluate a point mutation associated with the a16H allele within the region encoding agouti's putative signal sequence and our results suggest that this mutation is sufficient to cause the a16H phenotype. Thus, in vitro mutagenesis followed by the generation of transgenic mice should allow us to identify important functional elements of the agouti protein.
Perry
W L
WL
Mammalian Genetics Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Hustad
C M
CM
Swing
D A
DA
Jenkins
N A
NA
Copeland
N G
NG
D000199:Actins / Q000235:genetics; D054366:Agouti Signaling Protein; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005796:Genes; D005804:Genes, Lethal; D006200:Hair Color / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics
C515182:ASIP protein, human; D000199:Actins; D054366:Agouti Signaling Protein; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C515183:a protein, mouse