Referral Center - Animal models of human genetic disease

描述(申请人提供)：现在有可能分离与遗传疾病有关的基因，并从潜在的分子错乱方面了解疾病的机制，遗传疾病的治疗有令人鼓舞的新前景，包括体细胞基因和干细胞治疗。如果没有真正的(基因同源的，同源的)动物模型进行研究，人类患者的伦理和实际原因是不可能的，就不可能实现对人类患者遗传疾病的全面理解和治疗。小鼠的基因敲除技术提供了一个宝贵的来源，但需要更多的模型来进行研究，要求体型更大的长寿动物能够监测临床症状，以及那些表型更接近人类疾病的动物。在现有的近亲繁殖动物种群中存在大量此类疾病，可以在饲养员、兽医和其他对遗传疾病控制感兴趣的人的合作下进行研究。我们已经证明，通过提供一个可访问的中心来确定、验证、保存和分发这些人类遗传病模型，可以进一步利用这一资源。该项目的目标是继续作为国家转诊中心，识别、表征和提供新的和现有的大型人类遗传病动物模型用于研究。所寻求的模型主要在狗、猫和非人类灵长类动物中，涉及具有与人类患者相同的分子和临床表型的同源基因座缺陷。将与咨询委员会协商，强调为研究疾病发病机制和治疗方法提供新机会的模型。该中心将提供发现新的动物模型所需的临床、病理和分子遗传学研究，包括那些具有复杂遗传的动物模型，并建立它们与人类疾病的同源性。经过验证的模型将以DNA、细胞、冷冻精液和繁殖种群的形式象征性地向其他研究人员提供服务费用。我们还将继续为其他研究人员提供正常的狗和猫及其组织的资源，我们将提供一个项目，外部研究人员可以在我们的资源中心设施中进行狗和猫的实验，两者都是按服务收费的。

DESCRIPTION (provided by applicant): It is now possible to isolate genes involved in genetic diseases and understand disease mechanisms in terms of the underlying molecular derangements, and there are encouraging new prospects for therapy for genetic diseases, including somatic cell gene and stem cell therapies. The full scope of understanding and treating genetic diseases in human patients cannot be realized without authentic (gene-homologous, orthologous) animal models for studies not possible for ethical and practical reasons in human patients. Gene knockout technology in mice has provided a valuable source, but additional models are needed for studies requiring long-lived animals of larger size to be able to monitor clinical signs, and those with phenotypes more closely resembling the human diseases. A large reservoir of such diseases is present in existing inbred animal populations and can be studied with the cooperation of breeders, veterinarians, and others interested in genetic disease control. We have shown that this resource can be further utilized by providing an accessible Center to ascertain, verify, preserve, and distribute these models of human genetic disease. The objective of this project is to continue to serve as a National Referral Center to identify, characterize, and make available for research new and existing large animal models of human genetic disease. The models sought are primarily among dogs, cats, and non-human primates and involve defects in homologous gene loci having the same molecular and clinical phenotypes as in human patients. Models offering new opportunities to investigate disease pathogenesis and approaches to therapy will be emphasized in consultation with an Advisory Committee. The Center will provide the clinical, pathological, and molecular genetic studies required to discover novel animal models, including those with complex inheritance, and establish their homology with the human disorder. Verified models will be made available to other investigators at a nominal fee-for-service in the form of DNA, cells, frozen semen, and breeding stock. We will also continue to serve as a resource for normal dogs and cats and their tissues for other investigators, and we will offer a program where outside investigators can perform experiments in dogs and cats in our Resource Center facility, both on a fee-for-service basis.