EMBRYOLOGIC CONSEQUENCES OF TRISOY 16 IN MICE

TRISOY 16 对小鼠的胚胎学影响

• 批准号: 3317600
• 负责人: Mary L Oster-Granite
• 金额: $ 13.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3317600
• 关键词: Alzheimer's disease; Downs syndrome; biological models; chromosome aberrations; dendrites; early embryonic stage; electron microscopy; embryo /fetus death; embryo /fetus disorder; gene expression; histochemistry /cytochemistry; mammalian embryology; mature animal; mental retardation; microscopy; neuroanatomy; postnatal growth disorder; prosencephalon; silver impregnation; synapses; tissue mosaicism; trisomy

Specific genetic loci on mouse chromosome 16 (MMU16) are syntenic with genel located on human chromosome 21 (HSA21) specifically that portion of HSA21 associated with the phenotypic characteristics of Down Syndrome (DS) when present or expressed in the trisomic state (Ts21). The specific aim of this research proposal is to utilize mice with complete trisomy of MMU16 as model systems in which to examine the embryologic consequences of this trisomy. Both mental retardation and the premature onset of dementia clinically and neuropathologically indistinguishable form senile dementia of the Alzheimer's type (SDAT) are well established deleterious effects of human (Ts21). The pathogenesis and mechanism(s) by which these neurologic effects arise are unknown. Their elucidation requires the use of an animal model system with close genetic homology. Particular emphasis in these studies will be placed upon determining the extent to which neuroanatomic features characteristic of Ts21 are present in Ts16 mice. These features include altered numbers and distributions of microneurons and altered dendritic and synaptogenetic patterns in several portions of the neuraxis. In our examination of the neuraxes of Ts16 mice and chimeras composed of Ts16 cells at successive developmental stages, we will utilize Golgi, light and electron microscopic, and immunocytochemical methods. We will focus our examinations on the cerebellar cortex, hippocampus, portions of the cerebral cortices, and the basal forebrain. The use of chimeras is critical, since Ts16 fetuses die in utero before the differentiation of the neuraxis has been completed. The completion of a neuropathogenesis study of a mammalian trisomy will serve as basis for future studies unravelling the mechanism(s) by which these morphologic abnormalities arise and may eventually serve as an assay system for ameliorative therapeutic measures.

小鼠染色体16（MMU16）上的特定遗传基因座与 Genel位于人类染色体21（HSA21）上 HSA21与唐氏综合症（DS）的表型特征相关 当以三化状态（TS21）中存在或表达时。 具体目标 这项研究建议是利用MMU16的完整三体性的小鼠 作为检查此类胚胎学后果的模型系统 三体。 智力低下和痴呆过早发作 临床和神经病理学上无法区分的形式老年痴呆 阿尔茨海默氏症类型（SDAT）是确定的有害影响 人（TS21）。 这些神经系统的发病机理和机制 效果尚不清楚。 他们的阐明需要使用动物 具有密切遗传同源性的模型系统。 这些特别强调 研究将在确定神经解剖学的程度上进行研究 TS16小鼠中存在TS21的特征。 这些功能 包括微神经元的数字和分布的变化和变化 在神经结构的几个部分中的树突状和突触遗传学模式。 在检查由TS16小鼠和嵌合体的神经检查中 TS16细胞在连续的发育阶段，我们将利用高尔基 和电子显微镜和免疫细胞化学方法。 我们将集中精力 我们对小脑皮层，海马，部分的检查 脑皮质和基础前脑。 嵌合体的使用是 关键，因为TS16胎儿在分化之前在子宫内死亡 神经术已完成。 神经病发生研究的完成 哺乳动物三体性将作为未来研究的基础 这些形态异常出现的机制，可能 最终充当改善治疗方法的测定系统。