REFERRAL CENTER--ANIMAL MODELS OF HUMAN GENETIC DISEASE

转诊中心--人类遗传病动物模型

基本信息

批准号：
2281651
负责人：
DONALD F PATTERSON
金额：
$ 35.41万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-20 至 1998-09-19
项目状态：
已结题

项目摘要

The increasing possibilities for treating genetic disorders in human patients by approaches ranging from gene product replacement to gene transfer have created an increasing need for animal models in which to investigate pathogenetic mechanisms and approaches to therapy. The large reservoir of naturally-occurring counterparts of human genetic disease in animals has not been adequately utilized, largely because of the lack of accessible centers providing the special studies needed to identify genetic disorders in animals and establish their homology with human genetic diseases. In previous grant periods, we have demonstrated the value of such a center. The objective of this project is to continue to provide a national referral center for the identification, characterization, and dissemination of useful new animal models of human genetic disease. Emphasis in this proposal will be on monogenic human inborn errors of metabolism potentially correctable by gene therapy. The animal models sought among various species including murine, feline, and canine, will be true homologs of these human diseases (involve homologous gene loci and have disease characteristics comparable to the human disease). The center will provide consultation and laboratory studies of promising new models, including detection and identification of abnormal metabolites, cytogenetics, and special pathologic studies of biopsies and postmortem specimens. Family and breeding studies will be used to define modes of inheritance. Established new models will be made available to the general biomedical community in the form of cell cultures, DNA, frozen semen, and breeding stock. In selected monogenic metabolic disorders where the gene has not been cloned in the model species, we will clone the normal and mutant cDNA, characterize the mutation, and make the normal cDNA available for gene transfer studies.

治疗人类遗传疾病的可能性越来越多通过从基因产物替代到基因的方法转移对动物模型的需求越来越多研究致病机制和治疗方法。大人类遗传疾病的自然疾病的水库在动物中尚未得到充分利用，主要是因为缺乏可访问中心提供的特殊研究以识别动物的遗传疾病并与人类建立同源性遗传疾病。在以前的赠款期间，我们已经证明了这种中心的价值。该项目的目的是继续提供国家转诊中心以识别，表征和传播有用的人类新动物模型遗传疾病。该提议的重点将放在单基因人类上代谢的天生错误可能通过基因治疗来纠正。这动物模型在包括鼠，猫和犬类将是这些人类疾病的真正同源物（涉及同源性基因基因座，具有与人类相当的疾病特征疾病）。该中心将提供咨询和实验室研究有希望的新模型，包括检测和识别异常代谢物，细胞遗传学和特殊病理研究活检和验尸标本。家庭和育种研究将是用于定义继承模式。建立的新型号将被制作以细胞的形式可供一般生物医学界培养物，DNA，冷冻精液和繁殖量。在选定的单基因中在模型中未克隆基因的代谢疾病物种，我们将克隆正常和突变的cDNA，以表征突变，并使正常cDNA可用于基因转移研究。