Maximizing the utilization of porcine animal models by development of a pygmy pig

描述（由申请人提供）：猪作为转化研究的杰出模型在生物医学界有着悠久的使用历史。随着体细胞核移植（SCNT）的发展，以及猪基因组测序的完成，现在可以产生并仔细分析各种人类疾病的转基因猪模型。这些包括囊性纤维化、皮肤癌、糖尿病、色素性视网膜炎、黄斑变性的现有猪模型，以及用于异种移植的各种猪。除此之外，目前正在生成大量模型。猪在生物医学研究中的价值已经得到了NCRR/NIH的认可，并建立了国家猪资源与研究中心（NSRRC）。因此，这是生物医学研究中一个有价值的新兴领域，将对基础和转化进展产生重大影响。不幸的是，这些有价值的转基因品系中的绝大多数是使用商业猪品种开发的。结果，动物生长到可以达到>500磅的大小。这使得住房和管理困难，因为大多数生物医学研究中心没有足够的设施，可以处理大型猪。因此，为了最大限度地利用这些有价值的品系，如果有一种系统可以在单次育种中容易地减小现有的大转基因品系的大小，这将是非常有利的。这可以通过将感兴趣的品系与携带转基因的转基因动物交配来实现，所述转基因以显性方式诱导侏儒症（不必培育成纯合性），而没有任何其他会影响所研究的表型的有害作用。我们建议开发和表征的转基因猪，可用于显着减少的大小，并增加现有的猪的生物医学模型的有用性。该项目的成功完成将影响多个NIH研究所，因为它可以应用于基本上所有现有的猪生物医学模型。

DESCRIPTION (provided by applicant): Swine have a long history of use in the biomedical community as outstanding models for translational research. With the development of somatic cell nuclear transfer (SCNT), and the completed sequencing of the porcine genome it is now possible to generate, and carefully analyze, a wide range of genetically modified porcine models of human disease. These includes existing porcine models of cystic fibrosis, skin cancer, diabetes, retinitis pigmentosa, macular degeneration, and a wide range of pigs for xenotransplantation. This is in addition to the large number of models that are being generated at present. The value of swine in biomedical research, has been recognized by the NCRR/NIH with the creation of the National Swine Resource & Research Center (NSRRC). Thus, this is a valuable and emerging field in biomedical research that will have significant impact in basic and translational advances. Unfortunately, the great majority of these valuable transgenic lines are developed using commercial swine breeds. As a result, the animals grow to sizes that can reach >500 lb. This makes housing and management difficult, as most biomedical research centers do not have adequate facilities that can handle large swine. Therefore, in order the maximize the use of these valuable lines it would be greatly advantageous if a system was available to easily reduce the size of existing large transgenic lines in a single breeding. This could be accomplished by mating the line of interest with a transgenic animal carrying a transgene that induces dwarfism in a dominant manner (does not have to be bred to homozygocity) without any other deleterious effects that would affect the phenotype being studied. We propose the development and characterization of a transgenic pig that can be used to significantly reduce the size, and increase the usefulness, of existing swine biomedical models. Successful completion of this project will affect multiple NIH institutes as it could be applied to essentiall all existing porcine biomedical models.