Miller M W, Duhl D M, Vrieling H, Cordes S P, Ollmann M M, Winkes B M, Barsh G S
Department of Pediatrics, Stanford School of Medicine, California 94305-5428.
Genes Dev. 1993 Mar;7(3):454-67. doi: 10.1101/gad.7.3.454.
The mouse agouti gene controls the deposition of yellow and black pigment in developing hairs. Several dominant alleles, including lethal yellow (Ay), result in the exclusive production of yellow pigment and have pleiotropic effects that include obesity and increased tumor susceptibility. In an interspecific backcross, we established genetic limits for the agouti gene and found that the Ay and the lethal non-agouti (ax) allele were not separated from a previously identified probe at the breakpoint of the Is1GsO chromosomal rearrangement. Using the Is1GsO probe, we isolated the agouti gene, and find that it has the potential to code for a secreted protein expressed in hair follicles and the epidermis, and that the level of expression correlates with the synthesis of yellow pigment. In the Ay mutation, there is a chromosomal rearrangement that results in the production of a chimeric RNA expressed in nearly every tissue of the body. The 5' portion of this chimeric RNA contains highly expressed novel 5' sequences, but the 3' portion retains the protein-coding potential of the nonmutant allele. We speculate that dominant pleiotropic effects of Ay are caused by ectopic activation of a signaling pathway similar to that used during normal hair growth.
小鼠刺鼠基因控制着发育中毛发里黄色和黑色色素的沉积。几个显性等位基因，包括致死黄色（Ay），会导致只产生黄色色素，并具有多效性作用，包括肥胖和肿瘤易感性增加。在种间回交中，我们确定了刺鼠基因的遗传界限，发现Ay和致死非刺鼠（ax）等位基因在Is1GsO染色体重排的断点处未与先前鉴定的探针分离。使用Is1GsO探针，我们分离出了刺鼠基因，发现它有可能编码一种在毛囊和表皮中表达的分泌蛋白，且表达水平与黄色色素的合成相关。在Ay突变中，存在一种染色体重排，导致在身体几乎每个组织中都表达一种嵌合RNA。这种嵌合RNA的5'部分包含高度表达的新5'序列，但3'部分保留了非突变等位基因的蛋白质编码潜力。我们推测，Ay的显性多效性作用是由一种类似于正常头发生长过程中使用的信号通路的异位激活引起的。
