Down syndrome: Bridging Genes and Neural Pathways

唐氏综合症：连接基因和神经通路

• 批准号: 7018513
• 负责人: JULIE RUTH KORENBERG
• 金额: $ 32.4万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-12 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7018513
• 关键词: Down; syndrome; Bridging; Genes; Neural

Affecting one in 700 live births, Down Syndrome is the major recognized genetic cause of mental retardation. It is, and expected to remain, a significant medical and social problem. While the neurological and behavioral phenotype of Down Syndrome and its genetic basis is complex, recent advances in technology, resources and knowledge mean that renal and effective progress in understanding Down Syndrome is now attainable. The immediate goal of this program project is the identification and characterization of the genes involved in the neurological, neurophysiological and behavioral phenotype of Down Syndrome. The long term goal is to apply this knowledge to the development of therapeutic interventions to ameliorate the cognitive deficits seen in Down Syndrome. The accomplishment of goals of this nature requires application of a broad spectrum of approaches, spanning molecular biology, mouse genetics and human behavior. Accordingly, this proposal will build upon the large body of information regarding Down Syndrome and human chromosome 21 compiled by this Program over the last fifteen years, and will extend its research focus in a clinically relevant direction. The specific aims of this program include: i)systematic identification and preliminary characterization of essentially all genes on chromosome 21 to determine best candidates for causation of the neurological and cognitive deficits of Down Syndrome; ii) construction and analysis of mouse models, both single gene transgenics and segmental trisomies, to test the roles of specific genes; iii) dissection of the cognitive deficits seen in individuals with Down Syndrome; iv) analysis of the behavior and physiology of relevant mouse mutants to refine understanding of the deficits seen in individuals with Down Syndrome and to define the limits of utility of mouse models; and v) design and testing in mice of new hypotheses and treatment approaches based on information obtained from the molecular, human behavior and mouse genetic data. Building on the past accomplishments and expertise of members of this program project and adding new directions and new areas of expertise makes attainment of these goals eminently feasible. Their success will add greatly to our understanding of neurological development in general and of mental retardation in Down syndrome in particular.

唐氏综合症是公认的主要疾病，影响七百个活产儿中就有一个 智力低下的遗传原因。它是并且预计将继续是 重大的医疗和社会问题。虽然神经系统和 唐氏综合症的行为表型及其遗传基础很复杂， 技术、资源和知识的最新进展意味着肾脏和 现在可以在了解唐氏综合症方面取得有效进展。 该计划项目的直接目标是识别和 涉及神经系统的基因的特征， 唐氏综合症的神经生理学和行为表型。长的 术语目标是将这些知识应用于治疗的开发 改善唐氏综合症认知缺陷的干预措施。 实现这种性质的目标需要广泛的应用 一系列方法，涵盖分子生物学、小鼠遗传学和 人类行为。因此，该提案将建立在大型机构的基础上 有关唐氏综合症和人类 21 号染色体的信息由 该计划在过去十五年中进行，并将扩展其研究 专注于临床相关方向。 该计划的具体目标包括： i) 系统识别和 21 号染色体上几乎所有基因的初步表征 确定神经和认知因果关系的最佳候选者 唐氏综合症的缺陷； ii) 小鼠模型的构建和分析， 单基因转基因和节段三体性，以测试 特定基因； iii）对认知缺陷的剖析 患有唐氏综合症的人； iv) 行为分析 相关小鼠突变体的生理学，以加深对 唐氏综合症患者的缺陷并确定限制 小鼠模型的实用性； v) 在小鼠中设计和测试新的 假设和治疗方法基于从获得的信息 分子、人类行为和小鼠遗传数据。 以该成员过去的成就和专业知识为基础 计划项目并添加新的方向和新的专业领域使得 实现这些目标是非常可行的。他们的成功将增加 极大地促进了我们对一般神经发育的理解 尤其是唐氏综合症患者的智力低下。