Differences in dorsal and ventral pigmentation result from regional expression of the mouse agouti gene.

The agouti coat color gene encodes a paracrine signaling molecule that controls the production of yellow and black pigment by melanocytes within hair follicles. Some agouti alleles affect the dorsum and ventrum independently, which has provided the basis for speculation that agouti gene action in different regions of the body is controlled by distinct genetic loci that are closely linked. Using a combination of cDNA cloning and RNA expression studies, we find that alternative isoforms of agouti mRNA contain different noncoding first exons located 100 kb apart, whose patterns of expression indicate independent control by regulatory elements that are either ventral specific or hair cycle specific. These results demonstrate that the apparent genetic complexity of the agouti locus is explained by the existence of multiple regulatory elements exerting control over a single coding sequence and provide a conceptual basis for understanding differences in dorsal and ventral hair coloration in many mammalian species. The ventral-specific agouti isoform represents an example of a transcript whose expression is restricted to ventral skin and provide an approach to investigate the mechanisms by which dorsal-ventral differences in gene expression are established and maintained. IMAGES:

刺鼠毛色基因（agouti coat color gene）编码一种旁分泌信号分子，该分子可调控毛囊内黑素细胞合成黄色与黑色色素。部分刺鼠等位基因可独立影响背部与腹部的毛色表型，这一现象催生了如下推测：刺鼠基因在身体不同区域的作用由紧密连锁的不同遗传基因座所调控。本研究通过互补DNA克隆（cDNA cloning）与RNA表达分析的联合手段，发现刺鼠mRNA的可变剪接异构体包含两段相距100千碱基对（kb）的不同非编码第一外显子，其表达模式表明，这两段外显子分别受腹侧特异性或毛囊周期特异性调控元件的独立调控。上述结果表明，刺鼠基因座表观上的遗传复杂性，实则由单个编码序列受多重调控元件控制所导致，同时也为理解众多哺乳动物物种背腹侧毛发毛色差异的分子机制提供了理论基础。腹侧特异性的刺鼠转录本是一类表达局限于腹部皮肤的转录产物的范例，该发现也为探究基因表达的背腹侧差异如何建立并维持的机制提供了研究途径。图像：