Expression and Function of Cone Pigment Genes

视锥细胞色素基因的表达和功能

• 批准号: 6436825
• 负责人: Jay Neitz
• 金额: $ 42.55万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6436825
• 关键词: Cercopithecidae; color visions; computer simulation; cone cell; electroretinography; functional /structural genomics; gene expression; gene induction /repression; genetic polymorphism; genetically modified animals; human genetic material tag; human tissue; laboratory mouse; male; messenger RNA; molecular genetics; nucleic acid sequence; polymerase chain reaction; sex chromosomes; vision disorders; visual photoreceptor; visual pigments

DESCRIPTION (From the Applicant's Abstract): Three visual pigments mediate trichromatic color vision in humans, Old World monkeys and apes. Genes that are nearly identical encode the middle- and long-wavelength sensitive pigments, abbreviated M and L, respectively. The M and L genes lie in a head-to-tail tandem array on the X-chromosome and were produced by a gene duplication event that is estimated to have occurred in the primate lineage about 35-60 million years ago. The short-wavelength sensitive pigment (S) is encoded by an autosome, and is estimated to have diverged from the ancestral M/L gene about 800-1 100 million years ago. The vast majority of cones in human and primate retina are either M or L cones, with only about 7 percent of cones being S. Among the L and M cones, each cell exclusively expresses only one pigment gene from the X-chromosome array. There are two fundamentally important unsolved mysteries regarding expression of the X-linked visual pigment genes that are the focus of this grant. First, do the M and L cones represent two distinct cell types, so that an M cone specific mechanism directs expression of M pigment, and an L cone specific mechanism directs expression of L pigment? In this scenario, the M and L cones are uniquely different, and the fact that they express different pigments is secondary to these other differences. Or, are the M and L cones one cell type in which there is a stochastic process that directs mutually exclusive expression of one of the X-chromosome pigment genes? In this scenario, the identity of the gene chosen for expression determines whether the cone will be an M or an L cone. The second mystery is, what determines which of the genes from an individual array are expressed? Recent evidence suggests that in arrays with 3 genes, the last gene in the array (3' most) is not expressed. But what about arrays with 4 genes, is the third gene expressed? Solving these two mysteries will have profound impact on our understanding of the fundamental biological processes that determine the organization of the photoreceptor mosaic, and of how neural circuits are wired to extract color information at the first synapse. Towards solving these mysteries we propose the following 4 specific aims: 1) To characterize the expression pattern of downstream genes, 2) To test the model for the mechanism that produces the high degree of L and M gene sequence polymorphism in humans implied from the observed expression pattern of downstream genes, 3) To conduct developmental and comparative studies to test the stochastic model; 4) To develop innovative models for directly testing the stochastic model.

描述(摘自申请者摘要)：三种视觉色素 人类、东半球猴子和类人猿的三色视觉。这些基因是 几乎相同的编码中波长和长波长敏感的颜料， 分别缩写为M和L。M和L的基因是头尾相连的 X染色体上的串联阵列，由基因复制事件产生 据估计，这种情况发生在灵长类世系中，大约有3500万到6000万 几年前。短波敏色素(S)由一种 常染色体，估计与祖先的M/L基因大约有分歧 8亿-11亿年前。人类和灵长类动物中的绝大多数锥体 视网膜是M视锥细胞或L视锥细胞，只有大约7%的视锥细胞是S视锥细胞。 在L锥体和M锥体中，每个细胞只表达一个色素基因 从X染色体阵列中。有两个根本上重要的问题尚未解决 关于X连锁视觉色素基因表达的谜团 这笔赠款的重点是。首先，M锥体和L锥体是否代表着两个截然不同的 细胞类型，因此M锥体特定的机制指导M的表达 L色素，而一个L锥特异的机制指导着L色素的表达？在……里面 在这种情况下，M锥体和L锥体是唯一不同的，事实是它们 表达不同的色素是次要的，而不是其他的差异。或者，是不是 M和L建立了一种细胞类型，在这种细胞类型中，有一个随机过程，它引导着 其中一个X染色体色素基因的互斥表达？在这 场景中，被选择用于表达的基因的身份决定是否 圆锥体将是M或L圆锥体。第二个谜团是，是什么决定了 来自单个阵列的基因被表达了吗？最近的证据表明 在有3个基因的阵列中，阵列中的最后一个基因(3‘最多)不表达。 但是有4个基因的阵列呢，第三个基因表达了吗？ 解开这两个谜团，将深刻影响我们对 决定组织结构的基本生物过程 光感受器马赛克，以及神经回路是如何连接以提取颜色的 在第一个突触上的信息。为了解开这些谜团，我们建议 以下4个具体目标：1)表征表达模式 下游基因，2)测试模型产生高密度脂蛋白的机制 L和M基因序列在人类中的多态程度 观察下游基因的表达模式，3)进行发育 并进行比较研究，对随机模型进行检验；4)开拓创新 用于直接检验随机模型的模型。