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

通过开发侏儒猪最大限度地利用猪动物模型

• 批准号: 8449028
• 负责人: Jorge A Piedrahita
• 金额: $ 21.25万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8449028
• 关键词: Affect; Alleles; Animal Experimentation; Animal Model; Animals; Artificial Insemination; Biocompatible Materials; Biomedical Research; Birth Weight; Body Size; Breeding; Canis familiaris; Cell Line; Characteristics; Communities; Complementary DNA; Cystic Fibrosis; Development; Diabetes Mellitus; Dwarfism; Estrus Detection; Family suidae; Female; Fertility; Fibroblasts; Gene Silencing; Generations; Genome; Germ Cells; Growth; HMGA2 gene; Health; Housing; Human; Institutes; Knock-out; Litter Size; Macular degeneration; Male Sterility; Measurement; Measures; Modeling; Morphology; National Center for Research Resources; Partner in relationship; Phenotype; Physiological; Pregnancy Rate; Puberty; Recording of previous events; Research; Resources; Retinitis Pigmentosa; Seminal fluid; Skin Cancer; System; Technology; Transgenes; Transgenic Animals; Transgenic Organisms; Translational Research; United States National Institutes of Health; Weight; Xenograft procedure; animal model development; base; cell motility; fetal; homologous recombination; human disease; improved; interest; male; offspring; postnatal; promoter; reproductive; research study; response; small hairpin RNA; somatic cell nuclear transfer; tool; vector

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.

描述（由申请人提供）：猪在生物医学界作为转化研究的杰出模型有悠久的使用历史。随着躯体细胞核转移（SCNT）的发展以及猪基因组的完整测序，现在可以生成并仔细分析人类疾病的广泛转基因猪模型。其中包括现有的囊性纤维化，皮肤癌，糖尿病，色素性视网膜炎，黄斑变性和多种猪的猪模型。这是目前正在生成的大量模型的补充。猪在生物医学研究中的价值已被NCRR/NIH认可，并创建了国家猪资源与研究中心（NSRRC）。因此，这是生物医学研究中有价值的新兴领域，将对基本和转化的进步产生重大影响。不幸的是，这些有价值的转基因线中的绝大多数是使用商业猪品种开发的。结果，这些动物的大小可能达到500磅。这使住房和管理变得困难，因为大多数生物医学研究中心都没有足够的设施来处理大猪。因此，为了最大程度地利用这些有价值的线条，如果可以轻松减小单个繁殖中现有大型转基因线的大小，则将非常有利。这可以通过将感兴趣的线与带有转基因的转基因动物配对，该转基因以主导方式诱导矮人（不必繁殖为纯合，而没有任何其他有害效应，都会影响所研究的表型。我们提出了转基因猪的开发和表征，可用于显着降低现有猪生物医学模型的大小和有用性。该项目的成功完成将影响多个NIH机构，因为它可以应用于所有现有的猪生物医学模型。