BEHAVIORS DISCRIMINATING AUTISM IN HUMANS AND ANIMALS

人类和动物自闭症的歧视行为

• 批准号: 6570876
• 负责人: MARK E STANTON
• 金额: $ 16.54万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570876
• 关键词: Downs syndrome; animal developmental psychology; attention; attention deficit disorder; autism; behavior test; biomarker; child (0-11); clinical research; conditioning; developmental neurobiology; disease /disorder etiology; disease /disorder model; eye movements; gene mutation; genetic models; hearing; human subject; laboratory mouse; laboratory rat; sensorimotor system; startle reaction; teratogens

Identification of the embryonic stage when injury can cause autism has led to the insight that the disorder is initiated by changes in the developing brain stem. The shortening of the hindbrain and loss of cranial nerve neurons in an animal model of the insult and a human cause of autism resemble features of the Hoxa-1 transgenic knockout mice. Thus, it is now possible to suggest a unifying hypothesis regarding the multiple etiologies of autism; We propose that teratogens and genetic defects lead to similar developmental changes in the brain stem because mutations of early developmental genes are the cause of familial cases and the teratogens which cause the disease act by interfering with the function of the same genes. The new finding that one of the candidate genes is abnormal in some cases of autism supports this hypothesis. In Project I. we shall create an animal model based on mutation of early developmental genes. We have already developed an animal model based on mutation of early developmental genes. We have already developed an animal model of teratologically-induced brain stem injury using valproic acid. Our plan to evaluate the behavior of animal models await the identification of tasks which a) discriminate autism from other developmental disabilities b) are applicable to animals c) are restricted in the functions required so that they might be connected to specific brain regions or systems. We have identified two tasks with the potential to meet these criteria- the conditioned eye-blink response in teratologic and genetic animal models of autism, and then apply the same task to human cases of autism and other developmental disabilities. A long-term goal is to develop an animal analogue of the attention task which will be applied to teratologic and genetic animal models of autism. The overall goal of this project is to provide tests of behavioral parallelism not only in our own animal models of autism, but in those developed by others.

识别胚胎阶段时受伤会导致自闭症的识别 关于这种疾病的见解是由发展的变化引发的 脑干。后脑的缩短和颅神经的丧失 侮辱和自闭症的动物模型中的神经元 类似于Hoxa-1转基因敲除小鼠的特征。因此，现在是 可能提出关于多个倍数的统一假设 自闭症的病因；我们提出培育剂和遗传缺陷铅 大脑茎的类似发育变化，因为 早期发育基因是家族病例的原因， 引起疾病作用的畸胎组通过干扰 相同的基因。候选基因之一的新发现是 在某些自闭症情况下，异常支持这一假设。在项目I。 我们将建立一个基于早期发育突变的动物模型 基因。我们已经开发了一种基于突变的动物模型 早期发育基因。我们已经开发了一种动物模型 使用丙戊酸引起的脑诱导的脑干损伤。我们的计划 评估动物模型的行为等待识别任务 a）将自闭症与其他发育障碍区分开来b） 适用于动物的c）在所需的功能中受到限制，以便 它们可能与特定的大脑区域或系统有关。我们有 确定了有可能满足这些标准的两个任务 - 有条件的眼光反应在畸形和遗传动物模型中 自闭症，然后将相同的任务应用于人类自闭症和其他案件 发育障碍。一个长期目标是发展动物 将应用于特性和的注意任务的类似物 自闭症的遗传动物模型。该项目的总体目标是 提供行为并行的测试，不仅在我们自己的动物模型中 自闭症，但在他人开发的人中。