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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.

摘要