Emerging links between premature ageing and defective DNA repair

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• 作者：Philip C. Hanawalt
• 关键词：Aging ; DNA repair ; Werner's syndrome ; Oxidative stress ; Unusual DNA structures
• 刊名：Mechanisms of Ageing and Development
• 出版年：2008
• 期刊代码：193_00476374
• 类别：med
• 出版时间：July-August 2008
• 卷：129
• 期：7-8
• 页码：503-505
• 文件大小：113 K

摘要

The vertebrate lens provides an excellent model to study the mechanisms that regulate terminal differentiation. Although fibroblast growth factors (FGFs) are thought to be important for lens cell differentiation, it is unclear which FGF receptors mediate these processes during different stages of lens development. Deletion of three FGF receptors (Fgfr1–3) early in lens development demonstrated that expression of only a single allele of Fgfr2 or Fgfr3 was sufficient for grossly normal lens development, while mice possessing only a single Fgfr1 allele developed cataracts and microphthalmia. Profound defects were observed in lenses lacking all three Fgfrs. These included lack of fiber cell elongation, abnormal proliferation in prospective lens fiber cells, reduced expression of the cell cycle inhibitors p27^kip1 and p57^kip2, increased apoptosis and aberrant or reduced expression of Prox1, Pax6, c-Maf, E-cadherin and -, β- and γ-crystallins. Therefore, while signaling by FGF receptors is essential for lens fiber differentiation, different FGF receptors function redundantly.