BEHAVIORS DISCRIMINATING AUTISM IN HUMANS AND ANIMALS

人类和动物自闭症的歧视行为

• 批准号: 6652283
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652283
• 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.

识别伤害可能导致自闭症的胚胎阶段已经导致 认识到这种疾病是由发育中的变化引起的 脑干。后脑缩短和脑神经丧失 动物模型中的神经元受到侮辱和人类自闭症的原因 类似于 Hoxa-1 转基因敲除小鼠的特征。因此，现在是 可以提出关于多重性的统一假设 自闭症的病因；我们认为致畸剂和遗传缺陷导致 由于突变导致脑干发生类似的发育变化 早期发育基因是家族性病例的原因， 导致疾病的致畸剂通过干扰细胞的功能来起作用 相同的基因。新发现候选基因之一是 某些自闭症病例中的异常支持了这一假设。在项目一中。 我们将创建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。我们已经开发出一种动物模型 使用丙戊酸致畸形引起的脑干损伤。我们的计划是 评估动物模型的行为等待任务的识别 其中 a) 将自闭症与其他发育障碍区分开来 b) 适用于动物 c) 所需功能受到限制，因此 它们可能与特定的大脑区域或系统相连。我们有 确定了两项有可能满足这些标准的任务 - 畸形和遗传动物模型中的条件性眨眼反应 自闭症，然后将相同的任务应用于自闭症和其他疾病的人类病例 发育障碍。长期目标是培育一种动物 注意力任务的类似物将应用于畸胎学和 自闭症的遗传动物模型。该项目的总体目标是 不仅在我们自己的动物模型中提供行为并行性测试 自闭症，但在其他人开发的自闭症中。