Vrieling H, Duhl D M, Millar S E, Miller K A, Barsh G S
Department of Pediatrics, Stanford School of Medicine, CA 94305-5428.
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5667-71. doi: 10.1073/pnas.91.12.5667.
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.
刺豚鼠毛色基因编码一种旁分泌信号分子，该分子控制毛囊内黑素细胞产生黄色和黑色色素。一些刺豚鼠等位基因独立影响背部和腹部，这为推测身体不同区域的刺豚鼠基因作用受紧密连锁的不同基因座控制提供了依据。通过结合cDNA克隆和RNA表达研究，我们发现刺豚鼠mRNA的可变异构体包含位于100 kb之外的不同非编码第一外显子，其表达模式表明受腹侧特异性或毛囊周期特异性调控元件的独立控制。这些结果表明，刺豚鼠基因座明显的遗传复杂性是由多个调控元件对单个编码序列的控制所解释的，并为理解许多哺乳动物物种背部和腹部毛色差异提供了概念基础。腹侧特异性刺豚鼠异构体代表了一种转录本的例子，其表达仅限于腹侧皮肤，并为研究基因表达的背腹差异建立和维持的机制提供了一种方法。
