DIFFERENTIAL EXPRESSION OF A NEW DOMINANT AGOUTI ALLELE (A(IAPY)) IS CORRELATED WITH METHYLATION STATE AND IS INFLUENCED BY PARENTAL LINEAGE
DIFFERENTIAL EXPRESSION OF A NEW DOMINANT AGOUTI ALLELE (A(IAPY)) IS CORRELATED WITH METHYLATION STATE AND IS INFLUENCED BY PARENTAL LINEAGE
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DOI：
10.1101/gad.8.12.1463
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发表时间：
1994-06-15
影响因子：
10.5
通讯作者：
WOYCHIK, RP
中科院分区：
文献类型：
--
作者：
MICHAUD, EJ;VANVUGT, MJ;WOYCHIK, RP
agglutinin基因通常赋予小鼠野生型毛色。在无糖蛋白基因座的显性突变导致多效性综合征，其特征在于被毛中过量的黄色色素、肥胖、非胰岛素依赖性糖尿病样病症和形成各种肿瘤的倾向。在这里，我们描述了一个新的显性突变在agglutinase基因座，其中脑池内A-粒子（IAP）已整合在一个反义方向立即5'的第一个编码外显子的基因。我们将该突变命名为A（IAP），其通过利用IAP 5'长末端重复序列（LTR）内的隐蔽启动子导致agglutinase基因的异位表达。A（iaproxin/）-小鼠的毛色范围从纯黄色到类似于野生型（假琼脂糖）的色素图案，并且这种突变表型的表达性随亲本遗传而变化。这些后代与黄色外套异位表达agreximRNA在高水平和表现出显着的肥胖，而pseudoagrexims小鼠表达agreximmRNA在一个非常低的水平，他们的体重没有不同的野生型同窝出生。提供的数据显示A（IAP）等位基因的差异表达性与插入的IAP 5' LTR的甲基化状态相关。这些数据进一步支持了这样的假设，即在agglutinin基因座的显性黄色突变中，野生型agglutinin编码序列的普遍表达是导致黄色毛色、肥胖、糖尿病和肿瘤发生的原因。
The agouti gene normally confers the wild-type coat color of mice. Dominant mutations at the agouti locus result in a pleiotropic syndrome that is characterized by excessive amounts of yellow pigment in the coat, obesity, a non-insulin-dependent diabetic-like condition, and the propensity to form a variety of tumors. Here, we describe a new dominant mutation at the agouti locus in which an intracisternal A-particle (IAP) has integrated in an antisense orientation immediately 5' of the first coding exon of the gene. This mutation, which we have named A(iapy), results in the ectopic expression of the agouti gene through the utilization of a cryptic promoter within the IAP 5' long terminal repeat (LTR). The coat color of A(iapy/)- mice ranges from solid yellow to a pigment pattern that is similar to wild type (pseudoagouti), and the expressivity of this mutant phenotype varies with parental inheritance. Those offspring with a yellow coat ectopically express agouti mRNA at high levels and exhibit marked obesity, whereas pseudoagouti mice express agouti mRNA at a very low level and their weights do not differ from wild-type littermates. Data are presented to show that the differential expressivity of the A(iapy) allele is correlated with the methylation status of the inserted IAP 5' LTR. These data further support the hypothesis that in dominant yellow mutations at the agouti locus, it is the ubiquitous expression of the wild-type agouti coding sequence that is responsible for the yellow coat color, obesity, diabetes, and tumorigenesis.