Discovering new genes involved in protective T-cell responses through the generation of mice with targeted mutations

通过培育具有靶向突变的小鼠，发现参与保护性 T 细胞反应的新基因

基本信息

批准号：
10042745
负责人：
Luis J Sigal
金额：
$ 23.4万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10042745
关键词：
Adopted Animals Antibodies Antigens Antiviral Agents Antiviral Response Area Autoimmune Diseases Biology Bone Marrow CD3 Antigens CD44 gene CD8-Positive T-Lymphocytes CD8B1 gene Cells Cessation of life Chimera organism Communicable Diseases Cytotoxic T-Lymphocytes Development Disease Enzymes Exons Flow Cytometry Future Gene Deletion Generations Genes Genetic Transcription Gonadal structure Grant Granzyme Hematopoietic Human Immune Immune System Diseases Immune response Immune system Immunologic Deficiency Syndromes Immunology Inbred BALB C Mice Infection Infectious Ectromelia Knowledge Leukocytes Liver LoxP-flanked allele Maintenance Malignant Neoplasms Mammalian Oviducts Memory Methods Modeling Mouse Pox Virus Mouse Strains Mus Mutation PTPRC gene Peripheral Play Population Proteins RNA Reporter Resistance Role Site Spleen Splenocyte Stains T cell response T-Cell Activation T-Cell Development T-Lymphocyte Tamoxifen Thymus Gland Vaccines Viral Drug Resistance Viral load measurement Virus Diseases Work cancer therapy combat cost cytotoxic differential expression experience gene discovery gene function genome editing hepatic necrosis high risk immune resistance improved in vivo infectious disease treatment innovation insight mouse model novel nucleic acid delivery pathogen prevent resistant strain response transcriptome sequencing translational impact vaccine effectiveness

项目摘要

Abstract T-cells play major functions to combat infectious diseases and cancer, are critical for the effectiveness of vaccines, and may have negative effects in various types of immune disorders. While many of the genes involved in T-cell responses have been identified, it is likely that many remain unknown. The discovery of these genes and their specific roles during in vivo immune responses could provide major advances in our understanding of the immune system and for the improvement of vaccines and/or treatment of infectious diseases, cancer, and various immune disorders. Here we propose to generate mice with T-cell deletions of genes whose transcription is perturbed in specific T-cell populations during protective anti-viral T-cell responses. Our hypothesis is that some of these genes will play essential roles in immune responses to pathogens and possible in cancer and various immune dysfunctions. The mouse models developed through this grant will provide new valuable information about the role of still little-known genes in the modulation of the anti-viral immune response and resistance to viral infection and may be the basis of future novel discoveries encompassing not only immunology but other areas of mammalian biology.

抽象的 T细胞发挥着重要的作用来打击传染病和癌症，对疫苗的有效性，可能在各种类型的免疫疾病中产生负面影响。尽管已经确定了许多与T细胞反应有关的基因，但许多人可能许多仍然未知。这些基因的发现及其在体内免疫期间的特定作用回应可以为我们对免疫系统的理解提供重大进步改善疫苗和/或治疗传染病，癌症和各种免疫疾病。在这里，我们建议用基因的T细胞缺失产生小鼠在保护性抗病毒T细胞期间，在特定的T细胞种群中转录会受到干扰回答。我们的假设是，其中一些基因将在免疫中起重要作用对病原体的反应，并可能在癌症和各种免疫功能障碍中。鼠标通过这笔赠款开发的模型将提供有关Still的作用的新宝贵信息抗病毒免疫反应和对病毒抗性的调节中鲜为人知的基因感染，可能是未来新颖发现的基础，不仅包括免疫学但是哺乳动物生物学的其他领域。