Animal Model Core

动物模型核心

基本信息

批准号：
8033346
负责人：
JOHN W OLNEY
金额：
$ 27.09万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2015-06-30
项目状态：
已结题

项目摘要

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.

动物模型核心（AMC）的总体目标是使用当前的专业知识华盛顿大学的调查人员和现有资源，通过促进新的动物模型的最佳发展和评估来改善智力和发育障碍者的生活。遗传异常和收购事件造成了大多数智力和发育障碍。动物模型是更好地了解这些条件并制定新的治疗，预防和最终治愈这些条件的新型策略的潜在工具。华盛顿大学研究缺血小鼠模型（5），结节硬化症（6）和溶酶体储存疾病（7-9），这表明了这种方法的力量。但是，模型仅适用于与发育障碍（例如脑瘫和自闭症）相关的许多条件中的少数模型。此外，尽管在许多情况下是已知原因，但智力和发育障碍的原因在20-90％的受影响下仍然未知（10）基因组，蛋白质组学和代谢组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出新的原因，例如脑叶酸缺乏症，该原因于2002年首次描述。（11）然而，对动物模型的需求将继续增长。到目前为止，华盛顿大学的个别调查人员在自己的实验室中开发了动物模型。他们自己发现了其他具有专业知识所需的研究人员，以帮助他们发展和评估模型。与这些调查人员的非正式讨论强调了特定个人之间的富有成果的合作，但也揭示了许多调查人员没有充分利用的事实大学可提供庞大的专业知识。这是AMC的一个关键目标是将几种研究方法汇总到一个具有凝聚力的功能单元中，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，我们确定了三个特定领域，以使研究界受益，因此将AMC分为三个子核： „遗传学/早期发展子核心：该子核心将使用遗传和生殖/早期发展技术帮助研究人员生成新的动物模型。它将有助于制定基于产前疗法，基因和干细胞疗法的策略。此外，它将更好地理解遗传修饰在IDD中疾病过程中的作用。 »行为子核心：该子核心将提供智力和发育障碍的新动物模型的行为评估。神经病理学子核心：该子核心将对智力和发育障碍的新动物模型提供神经病理学评估。