Identification and pharmacological analyses of eight naturally occurring caprine melanocortin-1 receptor mutations in three different goat breeds

文献类型： 外文期刊

第一作者： Xiong, Qi

作者： Xiong, Qi;Chen, Mingxin;Xiong, Qi;Chai, Jin;Tao, Ya-Xiong;Chai, Jin;Chai, Jin

作者机构：

关键词： Melanocortin-1 receptor;Goat;Natural mutation;Pharmacology;Coat color

期刊名称：GENERAL AND COMPARATIVE ENDOCRINOLOGY （ 影响因子：2.822； 五年影响因子：2.772 ）

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收录情况： SCI

摘要： The melanocortin-1 receptor (MC1R) belongs to the family of seven transmembrane G protein-coupled receptors and plays a central role in animal coat color. We have sequenced the full coding region of 954bp of the MC1R gene in 72 goats of three breeds with different coat colors and identified five missense mutations (K226E, F250V, G255D, V265I, and C267W) and one silent mutation (A61A), among which two haplotypes with complete linkage disequilibrium (A61A and F250V, G255D and V265I) were found. We performed detailed functional studies on the six single and two double mutations in transiently transfected HEK293T cells. We found that none of the mutants had decreased cell surface expression. However, all the mutants except A61A had decreased constitutive activities in the cAMP pathway. Five mutations (F250V, G255D, G267W, A61A/F250V, G255D/V265I) exhibited significant defects in ligand binding and consequent agonist-induced cAMP signaling and ERK1/2 activation. Additionally, K226E, with normal ligand binding affinity and cAMP signaling, showed a significant defect in ERK1/2 activation, exhibiting biased signaling. Co-expression studies showed that the five defective mutants did not affect wild-type MC1R signaling, hence they were not dominant negative. In summary, we provided detailed data of these goat MC1R mutations leading to a better understanding of the role of MC1R mutation and coat color in goats. (C) 2016 Elsevier Inc. All rights reserved.

分类号： R58

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