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Published as doi: 10.1096/fj.08-124321.
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(The FASEB Journal. 2009;23:2235-2243.)
© 2009 FASEB

Genetic loci that control the size of laser-induced choroidal neovascularization

Kei Nakai*,1, Michael S. Rogers*,1, Takashi Baba{dagger}, Taisaku Funakoshi{dagger}, Amy E. Birsner*, Dema S. Luyindula* and Robert J. D'Amato*,{ddagger},2

* Department of Surgery, Vascular Biology Program, Children’s Hospital, Boston, Massachusetts, USA;

{dagger} Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Tottori, Japan; and

{ddagger} Department of Ophthalmology, Harvard Medical School, Cambridge, Massachusetts, USA

2 Correspondence: Vascular Biology Program, Children’s Hospital Boston, Karp 11.210, 300 Longwood Ave., Boston, MA 02115, USA. E-mail: robert.damato{at}childrens.harvard.edu

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.


Key Words: quantitative trait locus • QTL • recombinant inbred • BXD







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