Genetic loci that control the size of laser-induced choroidal neovascularization
Genetic loci that control the size of laser-induced choroidal neovascularization
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DOI：
10.1096/fj.08-124321
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发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
D'Amato, Robert J.
中科院分区：
文献类型：
--
作者：
Nakai, Kei;Rogers, Michael S.;D'Amato, Robert J.
血管生成受刺激物和抑制物之间的平衡控制。我们建议，平衡，以及一般的敏感性内皮细胞对这些因素，不同的个体。事实上，我们已经发现，个别小鼠品系有显着不同的反应生长因子诱导的新血管形成。本实验室以前鉴定了影响由血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（FGF 2）诱导的角膜血管生成程度的数量性状位点（QTL）。为了研究脉络膜新生血管（CNV），失明的主要原因的遗传贡献，我们已经进行了类似的定位方法，以确定影响激光诱导的CNV在BXD系列的重组近交系小鼠品系的QTL。复合区间作图确定了2号和19号染色体上新的血管生成QTL，此外还确认了我们先前的角膜新生血管化QTL AngVq 1和AngFq 2。这两个QTL分别命名为AngCNVq 1和AngCNVq 2。新绘制的区域包含参与血管生成过程的几个候选基因，包括血小板反应蛋白1，δ样4，Bcl II修饰因子，磷脂酶C，β 2，肾上腺素能受体，β 1，肌动蛋白结合LIM蛋白1和集落刺激因子2受体，α。这些区域的差异可能控制个体对CNV的易感性。Nakai，K.，罗杰斯，M。美国，巴巴，T.，Funakoshi，T.，Birsner，A. E、Luyindula，D.美国，达马托河控制激光诱导的脉络膜新生血管大小的遗传基因座。FASEB J. 23，2235-2243（2009）
Angiogenesis is controlled by a balance between stimulators and inhibitors. We propose that the balance, as well as the general sensitivity of the endothelium to these factors, varies from individual to individual. Indeed, we have found that individual mouse strains have dramatically different responses to growth factor-induced neovascularization. Quantitative trait loci (QTLs), which influence the extent of corneal angiogenesis induced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2), were previously identified by our laboratory. To investigate the genetic contribution to choroidal neovascularization (CNV), a leading cause of blindness, we have undertaken a similar mapping approach to identify QTLs that influence laser-induced CNV in the BXD series of recombinant inbred mouse strains. Composite interval mapping identified new angiogenic QTLs on chromosomes 2 and 19, in addition to confirming our previous corneal neovascularization QTLs of AngVq1 and AngFq2. The new QTLs are named AngCNVq1 and AngCNVq2. The newly mapped regions contain several candidate genes involved in the angiogenic process, including thrombospondin 1, delta-like 4, BclII modifying factor, phospholipase C, beta 2, adrenergic receptor, beta 1, actin-binding LIM protein 1 and colony stimulating factor 2 receptor, alpha. Differences in these regions may control individual susceptibility to CNV.-Nakai, K., Rogers, M. S., Baba, T., Funakoshi, T., Birsner, A. E., Luyindula, D. S., D'Amato, R. J. Genetic loci that control the size of laser-induced choroidal neovascularization. FASEB J. 23, 2235-2243 (2009)