Viral Hepatitis
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 1, 2004; 10(21): 3141-3145
Published online Nov 1, 2004. doi: 10.3748/wjg.v10.i21.3141
Replication and gene expression of mutant hepatitis B virus in a transgenic mouse containing the complete viral genome with mutant s gene
Jun-Hui Ge, Le-Zhi Zhang, Jian-Xiu Li, Hong Liu, Hui-Min Liu, Jin He, Yu-Cheng Yao, Yong-Ji Yang, Hong-Yu Yu, Yi-Ping Hu
Jun-Hui Ge, Hui-Min Liu, Jin He, Hong-Yu Yu, Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
Le-Zhi Zhang, Department of Experimental Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Jian-Xiu Li, Hong Liu, Yu-Cheng Yao, Yong-Ji Yang, Yi-Ping Hu, Department of Cell Biology, Second Military Medical University, Shanghai 200433, China
Author contributions: All authors contributed equally to the work.
Supported by National Science Foundation of China, No. 396670669 and No.39970676; Keystone basic research program of STCM, No. 03DZ14023
Correspondence to: Hong-Yu Yu, Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Telephone: +86-21-63610109-73703 Fax: +86-21-25070291
Received: January 9, 2004
Revised: March 5, 2004
Accepted: March 12, 2004
Published online: November 1, 2004

AIM: To establish the transgenic mouse line harbouring complete hepatitis B virus (HBV) genome with mutant s gene (adr subtype).

METHODS: Transgenic mice were generated by microinjecting HBV genome into fertilized eggs. Integration, expression, replication of HBV gene and histological changes in transgenic mice were estimated by genomic DNA PCR, serum DNA PCR, Southern blot, ELISA, HE staining, immunohistochemistry and transmission electron microscopy. Transgenic mice with HBsAg positive in serum were bred and analyzed.

RESULTS: A total of 288 eggs survived from microinjections were transplanted into the oviducts of 13 pseudopregnant mice and 49 pups were produced. Twenty-six mice were identified to have the integrated HBV gene. Serum HBsAg and HBeAg were detected in 2 of 43 mice. HBsAg and HBcAg in cytoplasm or nuclei of hepatocytes were detected in 10 mice. Founders with HBsAg in serum were named lineages G145R-15 and G145R-18. Of the 16 F1 offsprings generated by G145R-15 founder, 12 were positive for HBV genome with PCR, 10 were positive for HBsAg and HBcAg with immunohistochemistry and 7 were positive for HBsAg and HBeAg with ELISA. Only 1 of 8 F1 offsprings generated by G145R-18 founder was survived and it was detected positive for HBV genome, HBsAg, HBcAg and HBeAg. Both of the two lineages had some pathological characteristics of mild chronic hepatitis B in the liver, such as swelling of hepatocytes and focal hepatocellular necrosis and parenchymal lymphomononuclear cell infiltrate.

CONCLUSION: Transgenic mice harbouring HBV with mutant s gene can be generated. The HBV genes are integrated in the transgenic mice genome and can be expressed, replicated, packaged and excreted. HBV DNA can be stably transmitted in the transgenic mice.

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