Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
PLoS One. 2011;6(7):e21858. doi: 10.1371/journal.pone.0021858. Epub 2011 Jul 14.
Variation in genetic background can significantly influence the phenotypic outcome of both disease and non-disease associated traits. Additionally, differences in temporal and strain specific gene expression can also contribute to phenotypes in the mammalian retina. This is the first report of microarray based cross-strain analysis of gene expression in the retina investigating genetic background effects. Microarray analyses were performed on retinas from the following mouse strains: C57BL6/J, AKR/J, CAST/EiJ, and NOD.NON-H2(-nb1) at embryonic day 18.5 (E18.5) and postnatal day 30.5 (P30.5). Over 3000 differentially expressed genes were identified between strains and developmental stages. Differential gene expression was confirmed by qRT-PCR, Western blot, and immunohistochemistry. Three major gene networks were identified that function to regulate retinal or photoreceptor development, visual perception, cellular transport, and signal transduction. Many of the genes in these networks are implicated in retinal diseases such as bradyopsia, night-blindness, and cone-rod dystrophy. Our analysis revealed strain specific variations in cone photoreceptor cell patterning and retinal function. This study highlights the substantial impact of genetic background on both development and function of the retina and the level of gene expression differences tolerated for normal retinal function. These strain specific genetic variations may also be present in other tissues. In addition, this study will provide valuable insight for the development of more accurate models for human retinal diseases.
遗传背景的差异会显著影响疾病和非疾病相关特征的表型结果。此外，不同的时间和特定品系的基因表达差异也可能导致哺乳动物视网膜的表型。这是首次报道基于微阵列的视网膜跨品系基因表达分析，以研究遗传背景的影响。在胚胎 18.5 天（E18.5）和出生后 30.5 天（P30.5）时，对以下小鼠品系的视网膜进行了微阵列分析：C57BL6/J、AKR/J、CAST/EiJ 和 NOD.NON-H2(-nb1)。在不同的品系和发育阶段之间，鉴定出了超过 3000 个差异表达的基因。通过 qRT-PCR、Western blot 和免疫组织化学验证了差异基因表达。鉴定出了三个主要的基因网络，它们的功能是调节视网膜或光感受器的发育、视觉感知、细胞运输和信号转导。这些网络中的许多基因都与视网膜疾病有关，如视力迟钝、夜盲症和锥杆营养不良。我们的分析显示了品系特异性的视锥细胞发育和视网膜功能的变化。本研究强调了遗传背景对视网膜发育和功能的巨大影响，以及正常视网膜功能所容忍的基因表达差异水平。这些特定于品系的遗传差异也可能存在于其他组织中。此外，本研究将为开发更准确的人类视网膜疾病模型提供有价值的见解。
