Complex Mouse Models of Age-related Macular Degeneration

描述（由申请人提供）：本K26中期职业研究者提案的目的是双重的。首先，它将提供支持和指导小鼠病理生物学领域的学员的手段。其次，它将为PI Caroline Zeiss提供巩固其在视网膜变性领域研究成果的手段。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在全面运作的代谢表型核心。她开发和指导比较医学的唯一的研究生课程的部分，最近，已经开发了一个新的实验动物病理学课程。这些新的资源，加上该科现有的资源，将为根据小鼠病理学家联合会最近提出的建议编制小鼠病理生物学正式培训大纲奠定基础。该提案的科学基础是开发年龄相关性黄斑变性（AMD）的小鼠模型，代表了PI既定研究领域的延续。最初的建议的第一个目标已经完成。因此，这次重新提交的重点是两个最近发现的与人类AMD相关的基因（CFH和HTRA 1）的多态性是否可以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，从而为学员提供了一个选择实验室来获得研究经验的机会。在Zeiss博士的指导下，学员将获得小鼠病理学的教学和实践经验，并将完成旨在出版的指导研究项目。几年来，对接受病理生物学原则培训的比较病理学家的需求已经很明显。这一需求推动了ACVP/STP兽医病理学研究员联盟等组织的发展。支持这一建议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。 公共卫生相关性（由申请人提供）：这个K26奖项题为“年龄相关性黄斑变性的复杂小鼠模型”的目的是双重的。首先，它将提供支持和指导小鼠病理生物学领域的学员的手段。其次，它将为PI Caroline Zeiss提供巩固其在视网膜变性领域研究成果的手段。该奖项为期三年，其成功的资助将每年支持一名学员，并为PI提供受保护的时间来巩固她的实验室并建立坚实的研究支持。

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.