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Titolo:
An agouti mutation lacking the basic domain induces yellow pigmentation but not obesity in transgenic mice
Autore:
Miltenberger, RJ; Mynatt, RL; Bruce, BD; Wilkison, WO; Woychik, RP; Michaud, EJ;
Indirizzi:
Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA Oak Ridge Natl Lab Oak Ridge TN USA 37831 fe Sci, Oak Ridge, TN 37831 USA Univ Tennessee, Biochem Cellular & Mol Biol Dept, Knoxville, TN 37996 USA Univ Tennessee Knoxville TN USA 37996 Biol Dept, Knoxville, TN 37996 USA Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA Glaxo Wellcome Inc Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 15, volume: 96, anno: 1999,
pagine: 8579 - 8584
SICI:
0027-8424(19990720)96:15<8579:AAMLTB>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
STIMULATING-HORMONE-RECEPTOR; IN-VIVO; MELANOCORTIN RECEPTORS; FRAMESHIFT MUTATION; ECTOPIC EXPRESSION; PROTEIN; GENE; ANTAGONIST; BINDING; FRAGMENT;
Keywords:
pheomelanin; melanocortin receptors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Michaud, EJ Oak Ridge Natl Lab, Div Life Sci, POB 2009,MS 8077, Oak Ridge,TN 37831 USA Oak Ridge Natl Lab POB 2009,MS 8077 Oak Ridge TN USA 37831 USA
Citazione:
R.J. Miltenberger et al., "An agouti mutation lacking the basic domain induces yellow pigmentation but not obesity in transgenic mice", P NAS US, 96(15), 1999, pp. 8579-8584

Abstract

Chronic antagonism of melanocortin receptors by the paracrine-acting agouti gene product induces both yellow fur and a maturity-onset obesity syndrome in mice that ubiquitously express wild-type agouti, Functional analysis of agouti mutations in transgenic mice indicate that the cysteine-rich C terminus, signal peptide, and glycosylation site are required for agouti activity in vivo. In contrast, no biological activity has been ascribed to the conserved basic domain, To examine the functional significance of the agoutibasic domain, the entire 29-aa region was deleted from the agouti cDNA, and the resulting mutation (agouti Delta basic) was expressed in transgenic mice under the control of the beta-actin promoter (BAPa Delta basic). Three independent lines of BAPa Delta basic transgenic mice all developed some degree of yellow pigment in the fur, indicating that the agouti Delta basic protein was functional in vivo. However, none of the BAPa Delta basic transgenic mice developed completely yellow fur, obesity, hyperinsulinemia, or hyperglycemia. High levels of agoutii\basic expression in relevant tissues exceeded the level of agouti expression in obese viable yellow mice, suggesting that suboptimal activity or synthesis of the agouti Delta basic protein,rather than insufficient RNA synthesis, accounts for the phenotype of the BAPa Delta basic transgenic mice, These findings implicate a functional role for the agouti basic domain in vivo, possibly influencing the biogenesis of secreted agouti protein or modulating protein-protein interactions that contribute to effective antagonism of melanocortin receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 15:18:47