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首页> 外文期刊>Investigative ophthalmology & visual science >Microarray analysis of iris gene expression in mice with mutations influencing pigmentation.
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Microarray analysis of iris gene expression in mice with mutations influencing pigmentation.

机译：基因芯片在影响色素沉着突变的小鼠中虹膜基因表达的微阵列分析。

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PURPOSE: Several ocular diseases involve the iris, notably including oculocutaneous albinism, pigment dispersion syndrome, and exfoliation syndrome. To screen for candidate genes that may contribute to the pathogenesis of these diseases, genome-wide iris gene expression patterns were comparatively analyzed from mouse models of these conditions. METHODS: Iris samples from albino mice with a Tyr mutation, pigment dispersion-prone mice with Tyrp1 and Gpnmb mutations, and mice resembling exfoliation syndrome with a Lyst mutation were compared with samples from wild-type mice. All mice were strain (C57BL/6J), age (60 days old), and sex (female) matched. Microarrays were used to compare transcriptional profiles, and differentially expressed transcripts were described by functional annotation clustering using DAVID Bioinformatics Resources. Quantitative real-time PCR was performed to validate a subset of identified changes. RESULTS: Compared with wild-type C57BL/6J mice, each disease context exhibited a large number of statistically significant changes in gene expression, including 685 transcripts differentially expressed in albino irides, 403 in pigment dispersion-prone irides, and 460 in exfoliative-like irides. CONCLUSIONS: Functional annotation clusterings were particularly striking among the overrepresented genes, with albino and pigment dispersion-prone irides both exhibiting overall evidence of crystallin-mediated stress responses. Exfoliative-like irides from mice with a Lyst mutation showed overall evidence of involvement of genes that influence immune system processes, lytic vacuoles, and lysosomes. These findings have several biologically relevant implications, particularly with respect to secondary forms of glaucoma, and represent a useful resource as a hypothesis-generating dataset.
机译：目的：几种眼部疾病累及虹膜，特别是眼白化病，色素弥散综合症和剥脱综合症。为了筛选可能导致这些疾病发病机理的候选基因，从这些疾病的小鼠模型中比较分析了全基因组虹膜基因的表达模式。方法：将具有Tyr突变的白化病小鼠的虹膜样品，具有Tyrp1和Gpnmb突变的易发生颜料分散的小鼠以及具有Lyst突变的脱落样综合征的小鼠与野生型小鼠的样品进行比较。所有小鼠均品系（C57BL / 6J），年龄（60天大）和性别（雌性）匹配。使用微阵列比较转录谱，并使用DAVID Bioinformatics Resources通过功能注释聚类描述差异表达的转录本。进行定量实时PCR以验证已识别变化的子集。结果：与野生型C57BL / 6J小鼠相比，每种疾病的环境在基因表达上均表现出统计学上的显着变化，包括白化irirides中差异表达的685个转录物，易分散色素的irides中403个和剥落性脱落物中460个。激怒。结论：功能注释聚类在过高表达的基因中尤为突出，白化病和易分散颜料的铱均显示出晶状体介导的应激反应的整体证据。来自Lyst突变小鼠的剥落样样物显示出涉及影响免疫系统过程，裂解液泡和溶酶体的基因的整体证据。这些发现具有若干生物学相关的含义，尤其是在青光眼的继发形式方面，并作为一种产生假设的数据集提供了有用的资源。

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