Targeting of genes in the mammalian genome

哺乳动物基因组中的基因靶向

基本信息

批准号：
7315258
负责人：
MARIO R CAPECCHI
金额：
$ 39.79万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-12-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7315258
关键词：
Address Adolescent Affect Alveolar Rhabdomyosarcoma Animal Model Applications Grants Biological Biological Process Cell Nucleus Child Childhood Classification Communities Complex Defect Development Disease Dissection Etiology Evaluation Ewings sarcoma Face Facial Expression Facial nerve nucleus Gene Targeting Genes Grant Human Human Biology Knockout Mice Left Life Maintenance Malignant Neoplasms Mediating Medicine Modality Modeling Modification Molecular Molecular Genetics Motor Motor Neurons Mus Muscle Mutagenesis Mutation Nerve Neurons Pathology Pathway interactions Patients Radiosurgery Research Role Specific qualifier value Standards of Weights and Measures Technology Therapeutic To specify United States National Institutes of Health Work base chemotherapy design desire human disease malignant muscle neoplasm mammalian genome mouse model neural circuit new technology outcome forecast research study sarcoma success synovial sarcoma tumor progression young adult

项目摘要

DESCRIPTION (provided by applicant): Gene targeting provides the means for creating mice with designed modifications in any chosen gene. This technology permits the evaluation of the function of any gene in the living mouse and the systematic dissection of the most complex biological processes. It can be used to generate animal models of any human disease in order to study its pathology at a level of detail not feasible in human patients, and for the development of new more effective therapies that are based on a molecular-genetic understanding of the disease. This grant will continue to emphasize the development of gene-targeting-based technologies for the study of human biology and medicine. The particular projects that will be pursued in this grant proposal through the use of gene targeting include: To determine the roles of Hox genes in building simple neural circuits, particularly those involving the facial and lumbar motor nuclei; and to model the human sarcomas, alveolar rhabdomyosarcoma, synovial sarcoma, and Ewing's sarcoma in the mouse. These are very aggressive cancers that principally affect children, adolescents, and young adults and do not respond satisfactorily to the current common therapeutic modalities of surgery, radiation, and chemotherapy. They are prime candidates for the development of new, more effective therapies based on an understanding of the molecular etiology responsible for the progression of each of these cancers.

描述（由申请人提供）：基因打靶提供了在任何选定基因中产生具有设计修饰的小鼠的方法。该技术可以评估活体小鼠中任何基因的功能，并系统地剖析最复杂的生物过程。它可用于生成任何人类疾病的动物模型，以便以人类患者无法实现的详细程度研究其病理学，并开发基于对该疾病的分子遗传学理解的新的更有效的疗法。这笔赠款将继续强调用于人类生物学和医学研究的基因靶向技术的开发。本拨款提案中将通过使用基因靶向进行的特定项目包括：确定 Hox 基因在构建简单神经回路中的作用，特别是涉及面部和腰部运动核的神经回路；并在小鼠中建立人类肉瘤、肺泡横纹肌肉瘤、滑膜肉瘤和尤文氏肉瘤的模型。这些是非常侵袭性的癌症，主要影响儿童、青少年和年轻人，并且对目前常见的手术、放疗和化疗等治疗方式的反应并不令人满意。基于对每种癌症进展的分子病因学的了解，它们是开发新的、更有效的疗法的主要候选者。