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R. C. Symons, M. E. Swaim, T. W. Lauer, P. A. Campochiaro; Genetic Control of Vaso-Obliteration in Mouse Oxygen Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5695.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the genetic control of susceptibility to oxygen induced retinopathy (OIR) in the mouse.
OIR was induced by exposing pups to an inspired oxygen concentration of 75% from day 7 post-delivery (P7) to P12. In this model, the retinal hyperoxia causes central retinal vaso-obliteration. When the pups are returned to a normoxic environment the hypoxic central retina expresses angiogenic factors which cause pathological neo-vascularization. C57BL/6 mice demonstrate a greater degree of obliteration of the central retinal vasculature than do BALB/c mice. The retinal avascular areas after 96 hours of normoxia were measured using digital fluorescence micrographs of whole-mounted, fixed retinas perfused with fluorescein-dextran. Every mouse was weighed when the angiography was performed. Avascular areas were investigated in BALB/c and C57BL/6 mice, and also in the available recombinant inbred strains between these parental lines.
At P16 C57BL/6 mice had avascular areas which were 2.5 fold greater than in BALB/c (2.2 ± 0.2 mm2 cf 0.88 ± 0.07 mm2; mean ± s.d; P < 0.0001). ANOVA showed that both weight (P < 0.0005) and recombinant inbred strain (P < 0.0005) were significantly associated with avascular area. Weight and avascular area were negatively correlated. Further analyses were performed using avascular areas adjusted for mouse weight using a linear regression equation. R/qtl was used for genetic mapping. Using the algorithm of Sen and Churchill, loci on two chromosomes were found to be associated with peak LOD scores of 2.71 and 3.00. Permutation testing was performed to derive an empirical test statistic distribution, and it was found that the 5% significance threshold corresponded to a LOD score of 3.21. Thus the linkage is not statistically significant.
Retinal avascular areas in the OIR model are under tight genetic control. However, no significant linkage as yet been determined. An F2 intercross is being bred to yield further information for mapping.
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