TFII-I, A candidate gene for Williams syndrome cognitive profile: Parallels between regional expression in mouse brain and human phenotype
TFII-I, A candidate gene for Williams syndrome cognitive profile: Parallels between regional expression in mouse brain and human phenotype
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DOI：
10.1016/j.neuroscience.2003.08.038
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Desiderio, S
中科院分区：
文献类型：
--
作者：
Danoff, SK;Taylor, HE;Desiderio, S
TFII-I是一种广泛表达的转录因子，其基因定位于人类染色体7q11.23的区间，该区间在Williams综合征(WS)中是常见的缺失。WS的临床表型包括精灵相、婴儿高钙血症、主动脉瓣上狭窄、听力亢进和智力低下。WS认知特征(WSCP)表现为视觉空间能力的差异性损害，而言语语言功能相对较弱。WS患者的精细图谱显示TFII-I基因缺失与WSCP密切相关。为了确定TFII-I半合子缺失导致WSCP的假设的合理性，我们研究了TFII-I在成年和胚胎小鼠大脑中的解剖分布。我们的研究表明，在发育早期，TFII-I在大脑中的表达广泛且几乎一致。在成人大脑中，TFII-I蛋白仅存在于神经元中。在小脑浦肯野细胞和海马区中间神经元中的表达水平最高。TFII-I的免疫反应性与相关蛋白TFII-IRD1不同，TFII-IRD1也定位于WS中缺失的人7号染色体区域。TFII-I在小鼠脑中的表达模式与人脑中已被证明在解剖学和功能上发生改变的人类WS的区域相似。这些观察结果与TFII-I基因缺失与WS中观察到的认知障碍有关的假设一致。(C)2004年IBRO。爱思唯尔有限公司出版。保留所有权利。
The gene for TFII-I, a widely expressed transcription factor, has been localized to an interval of human chromosome 7q11.23 that is commonly deleted in Williams syndrome (WS). The clinical phenotype of WS includes elfin facies, infantile hypercalcemia, supravalvular aortic stenosis, hyperacusis and mental retardation. The WS cognitive profile (WSCP) is notable for the differential impairment of visual-spatial abilities with relative sparing of verbal-linguistic function. Fine mapping of individuals with WS has revealed a close association between deletion of TFII-I and the WSCP. To determine the plausibility of the hypothesis that hemizygous deletion of TFII-I contributes to the WSCP, we have examined the anatomic distribution of TFII-I RNA and protein isoforms in brains from adult and embryonic mice.Our studies show that early in development, TFII-I expression is widespread and nearly uniform throughout the brain. In adult brain, TFII-I protein is present exclusively in neurons. Highest levels of expression are observed in cerebellar Purkinje cells and in hippocampal interneurons. TFII-I immunoreactivity is distinct from that of the related protein, TFII-IRD1, which is also localized to the region of human chromosome 7 deleted in WS. The expression pattern of TFII-I in mouse brain parallels regions in human brain which have been shown to be anatomically and functionally altered in humans with WS. These observations are consistent with the hypothesis that deletion of the gene for TFII-I contributes to the cognitive impairments observed in WS. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.