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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Establishment of a humanized ST6GAL1 mouse model for influenza research
Lyu Chao1, Han Feng2, Gao Qian3
1National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China.
Background:
This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.
Methods:
Humanized fragments, consisting of the endothelial cell-specific K18 promoter, human ST6GAL1-encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.
Results:
Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range.
Conclusion:
A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

