A biochemical function for attractin in agouti-induced pigmentation and obesity

Lin He; Teresa M. Gunn; Donna M. Bouley; Xin Yun Lu; Stanley J. Watson; Stuart F. Schlossman; Jonathan S. Duke-Cohan; Gregory S. Barsh

doi:10.1038/83741

A biochemical function for attractin in agouti-induced pigmentation and obesity

Lin He, Teresa M. Gunn, Donna M. Bouley, Xin Yun Lu, Stanley J. Watson, Stuart F. Schlossman, Jonathan S. Duke-Cohan, Gregory S. Barsh

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

Abstract

Agouti protein, a paracrine signaling molecule normally limited to skin, is ectopically expressed in lethal yellow (A^γ) mice, and causes obesity by mimicking agouti-related protein (Agrp), found primarily in the hypothalamus. Mouse attractin (Atrn) is a widely expressed transmembrane protein whose loss of function in mahogany (Atrn^mg-3J/Atrn^mg-3J) mutant mice blocks the pleiotropic effects of A^γ. Here we demonstrate in transgenic, biochemical and genetic-interaction experiments that attractin is a low-affinity receptor for agouti protein, but not Agrp, in vitro and in vivo. Additional histopathologic abnormalities in Atrn^mg-3J/Atrn^mg-3J mice and cross-species genomic comparisons indicate that Atrn has multiple functions distinct from both a physiologic and an evolutionary perspective.

Original language	English (US)
Pages (from-to)	40-47
Number of pages	8
Journal	Nature Genetics
Volume	27
Issue number	1
DOIs	https://doi.org/10.1038/83741
State	Published - 2001
Externally published	Yes

ASJC Scopus subject areas

Genetics

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title = "A biochemical function for attractin in agouti-induced pigmentation and obesity",

abstract = "Agouti protein, a paracrine signaling molecule normally limited to skin, is ectopically expressed in lethal yellow (Aγ) mice, and causes obesity by mimicking agouti-related protein (Agrp), found primarily in the hypothalamus. Mouse attractin (Atrn) is a widely expressed transmembrane protein whose loss of function in mahogany (Atrnmg-3J/Atrnmg-3J) mutant mice blocks the pleiotropic effects of Aγ. Here we demonstrate in transgenic, biochemical and genetic-interaction experiments that attractin is a low-affinity receptor for agouti protein, but not Agrp, in vitro and in vivo. Additional histopathologic abnormalities in Atrnmg-3J/Atrnmg-3J mice and cross-species genomic comparisons indicate that Atrn has multiple functions distinct from both a physiologic and an evolutionary perspective.",

author = "Lin He and Gunn, {Teresa M.} and Bouley, {Donna M.} and Lu, {Xin Yun} and Watson, {Stanley J.} and Schlossman, {Stuart F.} and Duke-Cohan, {Jonathan S.} and Barsh, {Gregory S.}",

note = "Funding Information: We thank P. Kim and R. Saxena for technical assistance; C. Hwu, M. Ollmann, K. Willert, B. Wilson and J. Xu for advice about experimental design and data presentation; Y. Chen for construction of transgenic mice; P. Budd and I. Jackson for the Dct promoter construct; and H. Lee for assistance with animal breeding and genotyping. This work was supported by grants to G.S.B. (DK-48506) and to S.J.W. (MH42251) from the National Institutes of Health, and by a American Heart Association Western States fellowship award to T.M.G. G.S.B. is an Associate Investigator of the Howard Hughes Medical Institute. L.H. carried out the protein interaction studies and T.M.G. carried out the genetic interaction experiments.",

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AU - He, Lin

AU - Gunn, Teresa M.

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AU - Lu, Xin Yun

AU - Watson, Stanley J.

AU - Schlossman, Stuart F.

AU - Duke-Cohan, Jonathan S.

AU - Barsh, Gregory S.

N1 - Funding Information: We thank P. Kim and R. Saxena for technical assistance; C. Hwu, M. Ollmann, K. Willert, B. Wilson and J. Xu for advice about experimental design and data presentation; Y. Chen for construction of transgenic mice; P. Budd and I. Jackson for the Dct promoter construct; and H. Lee for assistance with animal breeding and genotyping. This work was supported by grants to G.S.B. (DK-48506) and to S.J.W. (MH42251) from the National Institutes of Health, and by a American Heart Association Western States fellowship award to T.M.G. G.S.B. is an Associate Investigator of the Howard Hughes Medical Institute. L.H. carried out the protein interaction studies and T.M.G. carried out the genetic interaction experiments.

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A biochemical function for attractin in agouti-induced pigmentation and obesity

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