ABSTRACT
BACKGROUND:HLA-DRB1 is related to the pathogenesis of alergic rhinitis. Construction ofHLA-DRB1 gene knockout animal models not only elucidates the pathogenesis of alergic rhinitis, but also provides a good way for the elucidation of the pathogenesis of alergic rhinitis-related diseases. OBJECTIVE:To establish the HLA-DRB1gene knockout animal models. METHODS:Homozygous, wild-type and heterozygous mice were obtained by inbreeding of the heterozygous mice. Confirmed by gene and protein identification, 24 female wild-type (H2-eb1+/+) mice and 12 H2-eb1-/-mice aged 8 weeks were selected according to the random number table. 12 H2-eb1+/+ mice and 12 H2-eb1-/- mice were sensitized with ovalbumin to establish the mouse models of alergic rhinitis. Another 12 mice were sensitized with PBS as comparison. RESULTS AND CONCLUSION:Compared with the control mice, serum levels of ovalbumin-specific IgE and interleukin-4 were significantly increased, while serum level ofγ-interferon was significantly decreased in the mouse models of alergic rhinitis. Serum levels of IgE and interleukin-4 were lower, while serumγ- interferon level was higher, inH2-eb1-/-gene knockout mice of alergic rhinitis than those in the H2-eb1+/+ gene knockout wild-type mice. These results suggest thatH2-eb1 gene may play an important role in regulating Th1/Th2 imbalance in the pathogenesis of alergic rhinitis.
ABSTRACT
Background: H2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis [AR]. Construction of H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis
Objective: To establish the H2-Eb1 knockout model and investigate the H2-EB1 functions in H2-Eb1 knockout mice as a model of AR
Methods: The Cre/LoxP system and ES gene knockout technology were applied to create heterozygous H2-Eb1 [ +/- ] knockout mice and their offspring of knockout homozygous[-/-], heterozygous [ +/- ] and wild type [+/+]H2-Eb1 mice. After identification, offspring of heterozygous [ +/- ] and homozygous [-/-]H2-Eb1 knockout mice were randomly selected to establish AR models to demonstrate the role of H2-Eb1 in AR pathogenesis
Results: The H2-Eb1 knockout mice model was successfully established. The reproduction and feeding of the homozygous [-/-]H2-Eb1 knockout mice were successful. Compared with the control group, the serum OVA-IgE and IL-4 levels significantly increased, while IFN- gamma levels significantly dropped [p<0.05] in the experimental groups. For the two experimental groups, the homozygous [-/-] mice group had lower serum OVA-IgE and IL-4 levels, and higher IFN-gamma levels than their heterozygous [ +/- ] counterparts [p<0.05], concomitant with slighter allergic symptoms [gentle behavior and less eosinophils in nasal mucosa]
Conclusion: Our study demonstrated that knockout of H2-Eb1 gene could alleviate mouse AR Symptoms, indicating H2-Eb1 may play an important role in regulating Th1/Th2 balance during the pathogenesis of AR