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R.J. D'Amato, A. Birsner, M. Rogers; Genetic Loci That Control Vascular Endothelial Growth Factor Induced Corneal Angiogenesis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4752.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously shown a great diversity in the corneal neovascularization response between different inbred strains of mice. In this study we perform quantitative trait locus (QTL) mapping to identify the chromosomal location of the genes that control individual angiogenic responsiveness in recombinant inbred mice. Methods: We have determined the level of Vascular Endothelial Growth Factor (VEGF) induced corneal neovascularization in 80 inbred progeny of C57BL/6J x DBA/2J and C57BL/6J x A/J strain crosses. The angiogenic response was measured 6 days after the implantation of a slow release pellet into corneal micropockets. Results: Individual recombinant strains demonstrated a large difference in angiogenic response, which, in some instances, were greater or less than the parental strains. The range of phenotypic response was up to 10–fold. QTL analysis indicates that angiogenic responsiveness is a complex trait with several contributing loci. QTL for corneal neovascularization induced by VEGF were located on Chromosomes 2 and 10 by both composite interval mapping (CIM) and multiple interval mapping (MIM) (LOD scores 6.9 and 11.4 respectively leading to p<0.001 by permutation analysis). MIM also suggests the existence of multiple additional QTLs. On proximal chromosome 10 we have confirmed the existence of a QTL which segregates in both C57BL/6J x DBA/2J and C57BL/6J x A/J crosses using congenic and consomic mouse strains. Within the linked region only a small, 0.4 Mbp, segment of chromosome 10 exhibits haplotype that is shared by A/J and DBA/2J strains, but differs from C57BL/6J mice. This small region, which contains only two genes, appears to contain the polymorphism(s) responsible for this loci’s contribution to the phenotypic differences in these strains. Conclusions: A genetic trait controlling angiogenesis can be mapped to proximal chromosome 10 in inbred strains of mice. Similar polymorphisms in humans may play a role in angiogenesis dependent diseases including macular degeneration and diabetic retinopathy.
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