GENETICS OF LINEAGE DETERMINATION DURING EMBRYOGENESIS

胚胎发生过程中谱系决定的遗传学

• 批准号: 2199524
• 负责人: JOSEPH H. NADEAU
• 金额: $ 20.95万
• 依托单位: MONTREAL GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2199524
• 关键词: chromosome walking; congenital disorders; developmental genetics; disease /disorder model; gene duplication; gene expression; gene mutation; genetic mapping; genetic markers; genetic transcription; heterozygote; histogenesis; homozygote; in situ hybridization; laboratory mouse; mammalian embryology; northern blottings; nucleic acid sequence; polymerase chain reaction; pulsed field gel electrophoresis

The genetic control of pattern formation during embryogenesis and the genetic basis for sporadic congenital anomalies are two important problems in mammalian developmental genetics. An unusual mouse mutation called disorganization (Ds) provides an exceptional model for studying both problems. Ds disrupts the orderly processes of development and causes an exceptional variety of birth defects involving all three germ layers and most body parts. These defects include aplasia, malformation, or ectopic development of many body structures. Many of these appear to result from problems in establishing symmetry, perhaps by causing mirror-image duplications. Highly variable expression and very low penetrance found in mice with the Ds mutation are characteristic of many sporadic congenital anomalies in humans. The long-term goal is to use Ds as a model for studying pattern formation and factors that contribute to many sporadic birth defects. Three specific aims will be used to accomplish these goals: Specific Aim I Complete the genetic and physical map of the Ds locus. These maps are the foundation for identifying candidate genes. Specific Aim 2 Identify and characterize candidate genes by finding and genetically mapping transcribed sequences and by characterizing their expression patterns. Specific Aim 3 Test whether Ds affects pattern formation by causing symmetrical anomalies (e.g. mirror-image or parallel duplications). Mouse mutants that cause syndactylies or polydactylies will be used to mark specific digits. The occurrence and location of these digit anomalies will be examined in mice that are heterozygous (or homozygous) both for Ds and for each of these other mutations. We will also test whether Ds and these other loci are in the same developmental pathway by determining whether novel congenital anomalies occur in double heterozygotes (or homozygotes).

胚胎发生过程中模式形成的遗传控制和 零星先天性异常的遗传基础是两个重要问题 在哺乳动物发育遗传学中。 一个不寻常的小鼠突变称为 混乱（DS）提供了研究两者的非凡模型 问题。 DS破坏了有序的发展过程，并导致 涉及所有三个细菌层和 大多数身体部位。 这些缺陷包括Aplasia，畸形或异位 发展许多身体结构。 其中许多似乎是由 建立对称性的问题，也许是通过引起镜像图像 重复。 高度可变的表达和非常低的渗透率 DS突变的小鼠是许多零星先天性的特征 人类异常。长期目标是将DS用作模型 研究模式形成和导致许多零星的因素 出生缺陷。 将使用三个具体目标来实现这些目标： 具体目的，我完成了DS基因座的遗传和物理图。 这些地图是识别候选基因的基础。 特定目标2通过查找和来识别和表征候选基因 基因映射的转录序列，并通过表征其 表达模式。 特定目标3测试DS是否通过引起影响模式形成 对称异常（例如镜像图像或平行重复）。老鼠 引起联合基因或多伴侣的突变体将用于标记 具体数字。这些数字异常的发生和位置将 在DS和 对于每个其他突变。我们还将测试DS和这些是否 其他基因座通过确定是否处于相同的发展途径 新型先天异常发生在双重杂合子（或纯合子）中。