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A. M. Nystuen, Y. Yuan, C. E. Gilling, N. B. Haider; Strain Background Influences on Gene Expression: Implications in Retinal Morphology and Function. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4146.
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© ARVO (1962-2015); The Authors (2016-present)
It is well established that genetic background can significantly influence the phenotypic outcome of a disease. Further, genetic variation also accounts for variation observed in normal phenotypes. The purpose of this study is to identify strain specific variation in gene expression that correlates with phenotypic variations observed in diseased and normal retinas in five inbred strains of mice.
Microarray analysis was performed with embryonic (E) 18 and adult retinas from the following strains: C57BL6/J, AKR/J, CAST/EiJ, NOD.NON-H2nb-1, and rd7. Differential gene expression was confirmed by qRT-PCR, western blot, and immunohistochemistry. Histological examination and ERG analysis was performed on adult retinas from each strain to evaluate strain specific differences in retinal morphology and function.
Over 3000 differentially expressed genes were identified. These genes include transcription factors, cell cycle genes, visual processing genes, retinol metabolism genes, and several retinal disease associated genes. ERG analysis revealed reduced b-wave amplitude in CAST/EiJ mice correlating with drastic reduction in expression of a candidate gene associated with a similar phenotype in human retinal disease. Immunohistochemical analysis revealed variation in photoreceptor topography among strains.
Varying degrees of differential gene expression were observed including some genes that had negligible expression. Additionally, genes within a given pathway were similarly expressed in a given strain but varied across strains. Together, these studies revealed that of the differentially expressed genes identified, 5-10% had variable expression between any two normal inbred strains, less than 5% varied between c57BL6/J and rd7 retinas, and 10% were similarly expressed in all strains and varied between E18 and adult.
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