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 16 号染色体 (MMU16) 上的特定遗传位点与 基因位于人类 21 号染色体（HSA21）上，特别是 HSA21 与唐氏综合症 (DS) 表型特征相关 当以三体状态存在或表达时（Ts21）。 具体目标 该研究计划的目的是利用具有 MMU16 完全三体性的小鼠 作为模型系统来检查这种现象的胚胎学后果 三体性。 智力低下和痴呆症过早发病 临床和神经病理学上与老年性痴呆无法区分 阿尔茨海默氏症 (SDAT) 的有害影响是公认的 人类（Ts21）。 这些神经系统疾病的发病机制和机制 产生的影响尚不清楚。 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。 特别强调这些 研究将集中在确定神经解剖学的程度 Ts21 的特征在 Ts16 小鼠中也存在。 这些功能 包括改变微神经元的数量和分布以及改变 神经轴几个部分的树突和突触发生模式。 在我们对 Ts16 小鼠和嵌合体的神经轴的检查中， Ts16 细胞在连续的发育阶段，我们将利用高尔基体、光 以及电子显微镜和免疫细胞化学方法。 我们将重点 我们对小脑皮质、海马体以及大脑部分区域的检查 大脑皮层和基底前脑。 嵌合体的用途是 至关重要，因为 Ts16 胎儿在分化之前就在子宫内死亡 神经轴已经完成。 完成神经发病机制研究 哺乳动物三体性的研究将作为未来研究的基础 这些形态异常发生的机制以及可能的机制 最终作为改善治疗措施的测定系统。