A MOLECULAR-MODEL FOR THE GENETIC AND PHENOTYPIC CHARACTERISTICS OF THE MOUSE LETHAL YELLOW (A(Y)) MUTATION
A MOLECULAR-MODEL FOR THE GENETIC AND PHENOTYPIC CHARACTERISTICS OF THE MOUSE LETHAL YELLOW (A(Y)) MUTATION
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DOI：
10.1073/pnas.91.7.2562
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发表时间：
1994-03-29
影响因子：
11.1
通讯作者：
WOYCHIK, RP
中科院分区：
文献类型：
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作者：
MICHAUD, EJ;BULTMAN, SJ;WOYCHIK, RP
致死黄（A（y））是小鼠2号染色体上的一种突变，可导致许多显性多效性效应，包括毛色完全变黄、肥胖、胰岛素抵抗II型糖尿病以及发生各种自发性和诱导性肿瘤的倾向增加。此外，A（y）的纯合性导致植入前致死，其终止胚泡阶段的发育。A（y）突变是170-kb缺失的结果，该缺失去除了另一个称为Raly的基因的除启动子和非编码第一外显子之外的所有外显子，该基因与agglutinin处于相同的转录方向，并且定位在agglutinin基因3'端附近的280 kb处。我们提出了一个模型的A（y）等位基因的结构，可以解释与此突变相关的显性多效性效应，以及隐性致死性，这是无关的agglutinase基因。
Lethal yellow (A(y)) is a mutation at the mouse agouti locus in chromosome 2 that causes a number of dominant pleiotropic effects, including a completely yellow coat color, obesity, an insulin-resistant type II diabetic condition, and an increased propensity to develop a variety of spontaneous and induced tumors. Additionally, homozygosity for A(y) results in preimplantation lethality, which terminates development by the blastocyst stage. The A(y) mutation is the result of a 170-kb deletion that removes all but the promoter and noncoding first exon of another gene called Raly, which lies in the same transcriptional orientation as agouti and maps 280 kb proximal to the 3' end of the agouti gene. We present a model for the structure of the A(y) allele that can explain the dominant pleiotropic effects associated with this mutation, as well as the recessive lethality, which is unrelated to the agouti gene.