Transgenic Mouse Model of Chronic Beryllium Disease

Gordon, Terry

关键词: ANIMALS;    ANTIGENS;    BERYLLIUM;    DISEASES;    DOSE-RESPONSE RELATIONSHIPS;    GENES;    GENETICS;    LEUKOCYTES;    MICE;    POPULATIONS;    STRAINS;    TESTING;    TRANSGENIC MICE beryllium;    transgenic mice;   

DOI  :  10.2172/953218
RP-ID  :  DOE/RD832528
PID  :  OSTI ID: 953218
Others  :  TRN: US201003%%707

学科分类：环境科学（综合）

美国|英语

来源: SciTech Connect

【 摘 要 】

Animal models provide powerful tools for dissecting dose-response relationships and pathogenic mechanisms and for testing new treatment paradigms. Mechanistic research on beryllium exposure-disease relationships is severely limited by a general inability to develop a sufficient chronic beryllium disease animal model. Discovery of the Human Leukocyte Antigen (HLA) - DPB1Glu69 genetic susceptibility component of chronic beryllium disease permitted the addition of this human beryllium antigen presentation molecule to an animal genome which may permit development of a better animal model for chronic beryllium disease. Using FVB/N inbred mice, Drs. Rubin and Zhu, successfully produced three strains of HLA-DPB1 Glu 69 transgenic mice. Each mouse strain contains a haplotype of the HLA-DPB1 Glu 69 gene that confers a different magnitude of odds ratio (OR) of risk for chronic beryllium disease: HLA-DPB1*0401 (OR = 0.2), HLA-DPB1*0201 (OR = 15), HLA-DPB1*1701 (OR = 240). In addition, Drs. Rubin and Zhu developed transgenic mice with the human CD4 gene to permit better transmission of signals between T cells and antigen presenting cells. This project has maintained the colonies of these transgenic mice and tested the functionality of the human transgenes.