小鼠酪氨酸酶基因中脑内A颗粒插入导致的遗传性体细胞镶嵌现象。
Inherited somatic mosaicism caused by an intracisternal A particle insertion in the mouse tyrosinase gene.
作者信息
Wu M, Rinchik E M, Wilkinson E, Johnson D K
机构信息
Biology Division, University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences, 37831-8077, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):890-4. doi: 10.1073/pnas.94.3.890.
Abstract
A recessive, fully penetrant mutation (c(m1OR)) at the mouse albino locus that results in coat-color mottling has been characterized at the molecular level. Restriction mapping and DNA sequencing analyses provide evidence that mutants carry a 5.4-kb intracisternal A particle (IAP) element insertion upstream of the tyrosinase (Tyr) promoter. Northern blot analysis and reverse transcription-PCR results show that the tyrosinase gene is expressed at much lower levels in mutant than in wild-type mice. The mutant Tyr gene still retains the tissue-specific expression pattern, and the Tyr transcript is not initiated from the IAP long terminal repeat promoter. We propose that the IAP insertion isolates the promoter of the tyrosinase gene from upstream cis-acting regulatory elements, leading to a substantially decreased level of Tyr gene expression in mutants.
摘要
已在分子水平上对小鼠白化病基因座处导致毛色斑驳的隐性、完全显性突变（c(m1OR)）进行了表征。限制性图谱分析和DNA测序分析表明，突变体在酪氨酸酶（Tyr）启动子上游携带一个5.4 kb的脑内A颗粒（IAP）元件插入。Northern印迹分析和逆转录PCR结果显示，与野生型小鼠相比，突变体中酪氨酸酶基因的表达水平要低得多。突变的Tyr基因仍保留组织特异性表达模式，且Tyr转录本并非由IAP长末端重复启动子起始。我们认为，IAP插入使酪氨酸酶基因的启动子与上游顺式作用调控元件分离，导致突变体中Tyr基因表达水平大幅降低。
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