Animal Model Core

动物模型核心(AMC)的总体目标是利用当前 华盛顿大学的研究人员和现有资源，通过促进新的和现有的动物模型的最佳发展和评估，改善智力和发育障碍者的生活。 遗传异常和后天侮辱是大多数智力和发育障碍的原因。动物模型是更好地了解这些疾病并开发治疗、预防和最终治愈这些疾病的新策略的有力工具。华盛顿大学在缺氧缺血(5)、结节性硬化症(6)和溶酶体储存性疾病(7-9)的小鼠模型上的工作证明了这种方法的力量。然而，模型只适用于与发育障碍相关的许多疾病中的一小部分，如脑瘫和自闭症。此外，尽管在许多情况下原因是已知的，但20%-90%的受影响的人智力和发育障碍的原因仍然未知 基因组学、蛋白质组学和代谢组学方法将有助于缩小这一差距。同时，标准的生化方法将继续识别新的原因，如2002年首次描述的大脑叶酸缺乏。(11)然而，对动物模型的需求将继续增长。 到目前为止，华盛顿大学的个人研究人员在自己的实验室里开发了动物模型。他们自己找到了其他拥有所需专业知识的研究人员，帮助他们开发和评估他们的模型。与这些调查人员的非正式讨论突出了具体个人之间富有成效的合作，但也暴露了这样一个事实，即许多调查人员没有充分利用 这所大学拥有丰富的专业知识。因此，AMC的一个关键目标是将几种研究方法结合成一个有凝聚力的功能单元，以促进与智力和发育障碍相关的动物模型的开发和评估。通过这些讨论，我们确定了使研究界受益的三个具体领域，并因此将AMC划分为三个子核心： 遗传学/早期发育分核心：该分核心将协助研究人员使用遗传和生殖/早期发育技术产生新的动物模型。它将帮助制定以产前治疗、基因和干细胞治疗为基础的战略。此外，它还将促进更好地了解基因改造在IDD疾病过程中的作用。 行为分核心：这个分核心将提供对新的和现有的智力和发育障碍动物模型的行为评估。 ？神经病理分核心：该分核心将提供对新的和现有的智力和发育障碍动物模型的神经病理评估。

The overall objective of the Animal Models Core (AMC) is to use the expertise of current investigators and existing resources at Washington University to improve the lives of those with intellectual and developmental disabilities by promoting the optimal development and assessment of new and existing animal models. Genetic abnormalities and acquired insults account for most intellectual and developmental disabilities. Animal models are a potent tool for obtaining a better understanding of these conditions and developing novel strategies for treating, preventing, and ultimately curing these conditions. Work at Washington University on mouse models of hypoxia ischemia(5), tuberous sclerosis(6) and lysosomal storage diseases(7-9) demonstrates the power of this approach. However, models are available for only a few of the many conditions associated with developmental disability, such as cerebral palsy and autism. Moreover, although causes are known in many instances, the cause of intellectual and developmental disabilities remains unknown for 20-90% of affected individuals.(10) Genomic, proteomic, and metabolomic approaches will help narrow this gap. Simultaneously, standard biochemical approaches will continue to identify novel causes such as cerebral folate deficiency, which was first described in 2002.(11) Nevertheless, the need for animal models will continue to grow. Until now, individual investigators at Washington University developed animal models in their own laboratories. On their own, they found other investigators with the expertise needed to help them develop and assess their models. Informal discussions with these investigators highlighted fruitful collaborations between specific individuals, but also brought to light the fact that many investigators had not taken full advantage of the vast expertise available at the university. Thus, a key goal of the AMC is to bring together several research methodologies into a cohesive functional unit to facilitate the development and assessment of animal models with relevance to intellectual and developmental disabilities. Through these discussions, we identified three specific areas to benefit the research community and have thus divided the AMC into three subcores: ¿ Genetics/Early Development Subcore: This Subcore will assist investigators with the generation of new animal models using genetic and reproductive/early development techniques. It will assist the development of strategies based on prenatal therapies, gene and stem cell therapy. In addition, it will promote a better understanding of the role of genetic modification in disease processes in IDD. ¿ Behavior Subcore: This Subcore will provide behavioral assessment of new and current animal models of intellectual and developmental disability. ¿ Neuropathology Subcore: This Subcore will provide neuropathologlcal assessment of new and current animal models of intellectual and developmental disability.