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R.J. D'Amato, M. Rogers, R. Rohan, A. Birsner; Genetic Mapping of Angiogenesis Controlling Genes in Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2020.
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Purpose: We have previously shown a great diversity of angiogenic potential 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 could that control individual angiogenic potential in recombinant inbred mice. Methods: We have determined the basic Fibroblast Growth Factor (bFGF) and Vascular Endothelial Growth Factor (VEGF) induced angiogenic response in 30 recombinant inbred (RI) strains between C57BL/6J and DBA/2J (BXD). The angiogenic response was measured 5 days after the implantation of a slow release pellet into corneal micropockets. Results: Individual recombinant strains demonstrated a large difference in angiogenic response, which ranged from less than either of the parental strains to higher than either of the parental strains. This range of phenotypic response was up to 10 fold for bFGF and 3 fold for VEGF. QTL analysis indicates that the angiogenic response 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 of small effect. QTL for corneal neovascularization induced by bFGF were located on chromosome 8 and 13 (LOD scores 5.0 and 4.5). This genetic mapping is currently being refined and candidate genes screened in each region. In addition we are working to confirm the existence of these QTLs using recombinant congenic strains of mice. Conclusion: Genetic traits controlling angiogenesis can be mapped in inbred strains of mice. These genes may play a role in angiogenesis dependent diseases in humans including macular degeneration and diabetic retinopathy.
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