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

基本信息

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
项目类别：
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

项目摘要

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，现在可以生成并仔细分析各种人类疾病的转基因猪模型。这些包括现有的囊性纤维化、皮肤癌、糖尿病、色素性视网膜炎、黄斑变性的猪模型，以及用于异种移植的各种猪。这是目前正在生成的大量模型的补充。 NCRR/NIH 认识到了猪在生物医学研究中的价值，并成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培育的。结果，这些动物长到可以达到> 500磅。这使得饲养和管理变得困难，因为大多数生物医学研究中心没有足够的设施来处理大型猪。因此，为了最大限度地利用这些有价值的品系，如果有一个系统可以在单次育种中轻松地减小现有大型转基因品系的大小，那将是非常有利的。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，该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转基因猪，该转基因猪可用于显着减小现有猪生物医学模型的尺寸并提高其实用性。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。