Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome
Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome
复制标题
DOI：
10.1073/pnas.0600012103
复制
发表时间：
2006-02-28
影响因子：
11.1
通讯作者：
Collins, FS
中科院分区：
文献类型：
--
作者：
Varga, R;Eriksson, M;Collins, FS
患有Hutchinson-Gilford早衰症(HGPS)的儿童与正常衰老相关的一些症状急剧加速，最明显的是心血管疾病，最终导致心肌梗死和/或中风，通常在他们第二个十年的生命中。对于绝大多数病例，层蛋白A(LMNA)基因的从头突变是HGPS的原因。这种错义突变产生了一个神秘的剪接供体部位，它产生了一个突变层蛋白A蛋白，被称为“孕激素”，在其C末端附近有一个50-AA的缺失。我们已经创建了一个早衰症的小鼠模型，方法是产生携带人类细菌人工染色体的转基因动物，该染色体含有常见的HGPS突变。这些小鼠发展为大动脉中层血管平滑肌细胞的进行性丧失，其模式与HGPS儿童非常相似。这种小鼠模型应该被证明对测试这种破坏性疾病的实验疗法和探索一般的心血管疾病是有价值的。
Children with Hutchinson-Gilford progeria syndrome (HGPS) suffer from dramatic acceleration of some symptoms associated with normal aging, most notably cardiovascular disease that eventually leads to death from myocardial infarction and/or stroke usually in their second decade of life. For the vast majority of cases, a de novo point mutation in the lamin A (LMNA) gene is the cause of HGPS. This missense mutation creates a cryptic splice donor site that produces a mutant lamin A protein, termed "progerin," which carries a 50-aa deletion near its C terminus. We have created a mouse model for progeria by generating transgenics carrying a human bacterial artificial chromosome that harbors the common HGPS mutation. These mice develop progressive loss of vascular smooth muscle cells in the medial layer of large arteries, in a pattern very similar to that seen in children with HGPS. This mouse model should prove valuable for testing experimental therapies for this devastating disorder and for exploring cardiovascular disease in general.