A comparative analysis of C57BL/6J and 6N substrains; chemokine/cytokine expression and susceptibility to laser-induced choroidal neovascularization.

ABSTRACT

Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly. To study potential underlying mechanisms of AMD, animal models are utilized, focusing mostly on mice. Recently, genomic and phenotypic differences between the so-called control substrains, C57BL/6J and C57BL/6N, have been described in models of ocular and non-ocular diseases. In particular, the rd8 mutation of the Crb1 gene present in the C57BL/6N has been shown to impact certain ocular phenotypes and appears to augment phenotypes generally associated with inflammation. Here, we investigated angiogenic factor and cytokine expression using pathway arrays as well as the susceptibility to laser-induced choroidal neovascularization (CNV), a model of wet AMD, in the two substrains. Age-matched 3-month-old C57BL/6J and C57BL/6N animals differed in gene expression levels for angiogenic factors and cytokines, with 6N animals expressing higher levels of inflammatory markers than 6Js. Yet laser-induced CNV was comparable in size between the two substrains. This lack of difference in CNV size was correlated with a gene expression profile that was comparable between the two substrains, due to the fact that the degree of change in gene expression of inflammatory markers after CNV was blunted in 6N mice. In summary, significant gene expression differences exist between C57BL/6J and C57BL/6N animals, reinforcing the notion that appropriate litter-mate controls or genetic background controls need to be used. Contrary to our expectation, CNV was not augmented in 6N animals, suggesting that low chronic inflammation in the RPE might provide a level of pre-conditioning and protection against stress.