SOMATIC CELL GENETIC STUDIES OF DOWN SYNDROME

唐氏综合症影响了700个活产婴儿中的一个，是公认的主要疾病。 智力低下的遗传原因。它是，并预计将继续是，一个 严重医疗和社会问题。虽然神经和 唐氏综合征的行为表型及其遗传基础是复杂的， 技术、资源和知识的最新进展意味着肾脏和 在了解唐氏综合症方面取得了有效进展。 该计划项目的直接目标是确定和 参与神经系统的基因的特征， 唐氏综合征的神经生理和行为表型。长 长期目标是将这些知识应用于治疗药物的开发， 改善唐氏综合症患者认知缺陷的干预措施。 实现这种性质的目标需要广泛的 一系列的方法，跨越分子生物学，小鼠遗传学和 人类行为因此，本提案将以大机构 关于唐氏综合症和人类21号染色体的信息， 该计划在过去的15年，并将扩大其研究 专注于临床相关的方向。 该方案的具体目标包括：一）系统地查明和 初步鉴定了21号染色体上的基本上所有基因， 确定神经和认知功能障碍的最佳病因 唐氏综合征的缺陷; ii）小鼠模型的构建和分析， 单基因转基因和节段性三体，以测试的作用， 特定的基因; iii）解剖的认知缺陷， 患有唐氏综合症的个体; iv）行为分析， 相关小鼠突变体的生理学，以完善对 在唐氏综合症患者中观察到的缺陷， 小鼠模型的实用性;和v）设计和在小鼠中测试新的 根据从研究中获得的信息， 分子、人类行为和小鼠遗传数据。 根据本组织成员过去的成就和专门知识， 计划项目和增加新的方向和新的专业领域， 实现这些目标是完全可行的。他们的成功将使 对我们理解神经系统的发展， 尤其是唐氏综合症患者的智力低下。

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.