STRUCTURE AND FUNCTION OF ASP, THE HUMAN HOMOLOG OF THE MOUSE AGOUTI GENE
STRUCTURE AND FUNCTION OF ASP, THE HUMAN HOMOLOG OF THE MOUSE AGOUTI GENE
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DOI：
10.1093/hmg/4.2.223
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发表时间：
1995-02-01
影响因子：
3.5
通讯作者：
BARSH, GS
中科院分区：
文献类型：
--
作者：
WILSON, BD;OLLMANN, MM;BARSH, GS
小鼠无毛毛色基因编码一种新的旁分泌信号分子，其脉冲式表达在个体毛发中产生特征性的带状色素图案。几种自发性聚集基因等位基因可导致成年期肥胖和糖尿病，并为能量代谢的改变提供了重要的单基因动物模型。利用小鼠和人类之间保守的连锁群，我们已经克隆了人类同源的小鼠agglutinase基因从人类20号染色体酵母人工染色体已知含有S-腺苷高半胱氨酸水解酶（AHCY）。人类聚集蛋白基因，命名为聚集蛋白信号蛋白（ASP），编码一个132个氨基酸的蛋白质，其mRNA在睾丸、卵巢和心脏中表达，在肝脏、肾脏和包皮中表达水平较低。正如小鼠聚集蛋白与延伸基因（编码α-黑素细胞刺激激素[α-MSH]的黑素细胞受体）的相互作用所预测的那样，ASP在转基因小鼠中的表达产生黄色皮毛，ASP在细胞培养物中的表达阻断了α-MSH刺激的小鼠黑色素瘤细胞中cAMP的积累。ASP相对于20号染色体上其他基因座的定位排除了它作为MODY 1基因座的候选者，MODY 1基因座是一种负责一种形式的早发性非胰岛素依赖型糖尿病或年轻人的成熟型糖尿病的基因。ASP在人体组织中的表达表明，在不表现出带状毛发特征表型的物种中，agglutinase同系物具有功能。
The mouse agouti coat color gene encodes a novel paracrine signaling molecule whose pulsatile expression produces a characteristic pattern of banded pigment in individual hairs. Several spontaneous agouti alleles produce adult-onset obesity and diabetes, and have provided important single-gene animal models for alterations in energy metabolism. Utilizing linkage groups conserved between mice and humans, we have cloned the human homolog of the mouse agouti gene from a human chromosome 20 yeast artificial chromosome known to contain S-adenosyl homocysteine hydrolase (AHCY). The human agouti gene, named Agouti Signaling Protein (ASP) encodes a 132 amino acid protein, the mRNA for which is expressed in testis, ovary, and heart, and at lower levels in liver, kidney, and foreskin. As predicted by the interactions of mouse agouti with the extension gene (which encodes the melanocyte receptor for alpha-melanocyte stimulating hormone [alpha-MSH]), expression of ASP in transgenic mice produces a yellow coat, and expression of ASP in cell culture blocks the alpha-MSH-stimulated accumulation of cAMP in mouse melanoma cells. The localization of ASP relative to other loci on chromosome 20 excludes it as a candidate for the MODY1 locus, a gene responsible for one form of early-onset non-insulin-dependent diabetes mellitus or maturity-onset diabetes of the young. The expression of ASP in human tissues suggests a function for agouti homologs in species that do not exhibit the characteristic phenotype of banded hairs.