Complex Mouse Models of Age-related Macular Degeneration

描述（由申请人提供）：这个K26中期职业调查员提案的意图是双重的。首先，它将为小鼠病理生物学领域的学员提供支持和指导。其次，它将为PI Caroline Zeiss提供巩固她在视网膜变性领域的研究成果的手段。Caroline Zeiss是一名执业兽医病理学家，在视网膜变性领域进行独立资助的研究（最近通过成功的R21提案）。此外，她还开发并指导了耶鲁大学医学院的小鼠病理表型核心以及现已完全运作的代谢表型核心。她开发并指导了比较医学部门唯一的研究生课程，最近又开发了一门新的实验动物病理学课程。这些新资源，连同科内已有的资源，将根据小鼠病理学家协会最近提出的建议，为小鼠病理生物学的正式培训大纲提供基础。该提案的科学基础是开发老年性黄斑变性（AMD）的小鼠模型，并代表了PI已建立的研究领域的延续。最初提议的第一个目标已经实现。因此，此次重新提交的重点是最近发现的与人类AMD相关的两个基因（CFH和HTRA1）的多态性是否会在小鼠中诱导该疾病。此外，还包括其他视觉研究实验室作为合作者，从而为受训者提供了获得研究经验的实验室选择。在蔡司博士的指导下，学员将获得小鼠病理学的教学和实践经验，并将完成一个旨在发表论文的指导研究项目。几年来，对受过病理原理训练的比较病理学家的需求已经很明显。这一需求为ACVP/STP兽医病理学研究员联盟等组织的发展提供了动力。这项建议的支持将为具有兽医病理学经验的学员提供机会，使他们在比较小鼠病理学和表型分析以及研究方法方面获得广泛的经验。

DESCRIPTION (provided by applicant): The intent of this K26 Mid Career Investigator proposal is twofold. First, it will provide the means to support and mentor trainees in the field of mouse pathobiology. Second, it will provide the PI, Caroline Zeiss, with the means to consolidate her research effort in the area of retinal degeneration. Caroline Zeiss is a practicing veterinary pathologist conducting independently funded research (most recently via a successful R21 proposal) in the area of retinal degeneration. In addition, she developed and directs the Mouse Pathologic Phenotyping Core at Yale University School of Medicine as well as its now fully operational Metabolic Phenotyping Core. She developed and directs the Section of Comparative Medicine's only graduate course, and more recently, has developed a new Laboratory Animal Pathology course. These new resources, together with those already available within the Section, will provide the basis for a formal training syllabus in mouse pathobiology in accordance with that recently proposed by the Mouse Pathologist's Consortium. This scientific basis of this proposal is to develop murine models for age-related macular degeneration (AMD), and represents the continuation of the PI's established research field. The first aim of the original proposal has been completed. Therefore this resubmission focuses whether polymorphisms in two recently discovered genes (CFH and HTRA1) that are associated with AMD in humans can induce the disease in mice. Further, additional vision research laboratories have been included as collaborators, thus providing the trainee a choice of laboratories in which to obtain research experience. Under guidance of Dr. Zeiss, trainees will obtain didactic and hands-on experience in mouse pathology, and will complete a mentored research project aimed at generating a publication. The need for comparative pathologists trained in pathobiologic principles has been evident for several years now. This need has provided the impetus for development of organizations such as the ACVP/STP Coalition for Veterinary Pathology Fellows. Support of this proposal would provide opportunities for trainees with experience in veterinary pathology to gain broad experience in comparative mouse pathology and phenotyping as well in research methodology. PUBLIC HEALTH RELEVANCE (provided by applicant): The purpose of this K26 award entitled "Complex mouse models of age-related macular degeneration" is twofold. First, it will provide the means to support and mentor trainees in the field of mouse pathobiology. Second, it will provide the PI, Caroline Zeiss, with the means to consolidate her research effort in the area of retinal degeneration. The award spans three years, and its successful funding will support one trainee per year, and provide protected time for the PI to consolidate her lab and establish solid research support.