Molecular and pharmacological characterization of dominant black coat color in sheep
Molecular and pharmacological characterization of dominant black coat color in sheep
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DOI：
10.1007/s003359900939
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发表时间：
1999-01-01
期刊：
影响因子：
2.5
通讯作者：
Cone, RD
中科院分区：
文献类型：
--
作者：
Våge, DI;Klungland, H;Cone, RD
预测绵羊的显性黑色被毛是由延伸位点的等位基因E-D引起的。最近的研究表明，该基因编码黑素细胞刺激激素受体（MC 1-R）。在小鼠和狐狸中，MC 1-R编码区中自然发生的突变产生了一种组成性激活的受体，该受体将黑素细胞内的黑素合成转换为真黑素，这解释了表型上观察到的黑色毛色。在绵羊中，我们已经确定了位置73的Met->Lys突变（M73 K）以及位置121的Asp -> Asn变化（D121 N），显示了在家族谱系中与显性黑色毛色的完全共分离。当引入相应的小鼠受体（mMC 1-R）进行药理学分析时，只有M73 K突变显示出组成性激活，然而，小鼠受体中对应于D121的位置是高亲和力配体结合所必需的。M73 K变化的药理学特征与忧郁小鼠中的组成型活性E92 K突变和阿拉斯加银狐中的C123 R突变相比是独特的，表明M73 K变化通过与这些先前表征的突变不同的机制激活受体。
Dominant black coat color in sheep is predicted to be caused by an allele E-D at the extension locus. Recent studies have shown that this gene encodes the melanocyte stimulating hormone receptor (MC1-R). In mouse and fox, naturally occurring mutations in the coding region of MC1-R produce a constitutively activated receptor that switches the synthesis from phaeomelanin to eumelanin within the melanocyte, explaining the black coat color observed phenotypically. In the sheep, we have identified a Met-->Lys mutation in position 73 (M73K) together with a Asp --> Asn change at position 121 (D121N) showing complete cosegregation with dominant black coat color in a family lineage. Only the M73K mutation showed constitutive activation when introduced into the corresponding mouse receptor (mMC1-R) for pharmacological analysis, however, the position corresponding to D121 in the mouse receptor is required for high affinity ligand binding. The pharmacological profile of the M73K change is unique compared to the constitutively active E92K mutation in the sombre mouse and C123R mutation in the Alaska silver fox, indicating that the M73K change activates the receptor via a mechanism distinct from these previously characterized mutations.