Humanized MC1R transgenic mice reveal human specific receptor function.

Humanized MC1R transgenic mice reveal human specific receptor function. Research Abstract Details 

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Humanized MC1R transgenic mice reveal human specific receptor function. Abstract Text:

Ian J Jackson,Peter S Budd,Margaret Keighren,Lisa McKie,Ian J Jackson,Peter S Budd,Margaret Keighren,Lisa McKie,

The melanocortin receptor, MC1R, is a key regulator of pigmentation in mammals, and is necessary for production of dark eumelanin pigment. Human MC1R variants with reduced or absent function are associated with red hair; mouse mutants result in yellow fur. Previous reports indicate differences between mouse and human receptors in their sensitivity to, and requirement for, alphaMSH agonist. We have generated a transgenic mouse model in which coat pigmentation is mediated solely by human MC1R. Although the hair pigment pattern is superficially normal, we show the human receptor is more sensitive to exogenous ligand than mouse Mc1r. Furthermore, although the endogenous receptor antagonist, agouti signalling protein, blocks activation of human MC1R, its action is unlike that on the mouse receptor in that it does not generate an inverse signal. In transfected cells, both receptors show ligand independent signalling. However, in transgenic mice, the human receptor does not elicit significant eumelanin synthesis in absence of ligand, in contrast to the mouse receptor which gives normal eumelanogenesis without ligand. Thus, the mouse model recapitulates the observation that humans mutated in POMC, the melanocortin precursor gene, lack eumelanin and have red hair. We suggest this apparent paradox can be explained by the much lower receptor number expressed in human versus mouse melanocytes, resulting in a much lower endogenous signalling in vivo.

Humanized MC1R transgenic mice reveal human specific receptor function. Publishing Authors By Initials

IJ Jackson,PS Budd,M Keighren,L McKie,IJ Jackson,PS Budd,M Keighren,L McKie,

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Humanized MC1R transgenic mice reveal human specific receptor function. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human molecular genetics

VOLUME: 16

Page Numbers: 2341-8

Journal Abbreviation: Hum. Mol. Genet.

ISSN: 0964-6906

DAY: 25

MONTH: 07

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 9208958

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Grant and Affiliation Information for Humanized MC1R transgenic mice reveal human specific receptor function.

AFFILIATION: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK. ian.jackson@hgu.mrc.ac.uk

Country: England

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MEDLINETA: Hum Mol Genet

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