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Báo cáo khoa học: Development of an HSV-tk transgenic mouse model for study of liver damage

The herpes simplex virus thymidine kinase⁄ganciclovir (HSV-tk⁄GCV) sys-tem that selectively depletes cells expressing HSV-tk upon treatment with GCV has provided a valuable tool for developing a new animal model expressing the desired tissue damage. In this paper, an HSV-tk vector with an albumin promoter⁄enhancer was constructed. Based on the favourable killing effect on Hep-G2 cells by the recombinant construct, the HSV-tk transgenic mouse strains were developed. | ềFEBS Journal Development of an HSV-tk transgenic mouse model for study of liver damage Yan Zhang Shu-Zhen Huang Shu Wang and Yi-Tao Zeng Shanghai Institute of MedicalGenetics Shanghai Children s Hospital Shanghai Jiao Tong University People s Republic of China Keywords albumin promoter enhancer animal model ganciclovir herpes simplex virus thymidine kinase inducible liver-specific disease Correspondence Y.-T. Zeng Shanghai Institute of Medical Genetics Shanghai Children s Hospital Shanghai Jiao Tong University Shanghai 200040 People s Republic of China Fax 86 21 6247 5476 Tel 86 21 6247 2308 E-mail ytzeng@stn.sh.cn Received 13 January 2005 revised 23 February 2005 accepted 7 March 2005 doi 10.1111 j.1742-4658.2005.04644.x The herpes simplex virus thymidine kinase ganciclovir HSV-tk GCV system that selectively depletes cells expressing HSV-tk upon treatment with GCV has provided a valuable tool for developing a new animal model expressing the desired tissue damage. In this paper an HSV-tk vector with an albumin promoter enhancer was constructed. Based on the favourable killing effect on Hep-G2 cells by the recombinant construct the HSV-tk transgenic mouse strains were developed. One strain of the TK transgenic mouse TK5 was studied intensively. Integration of the target gene was confirmed primarily by PCR. Fluorescence in situ hybridization following G-banding analysis demonstrated that the insertion site was located at 2F1-G3. The hepatocyte-specific transcription and expression of HSV-tk was verified by reverse transcription RT -PCR as well as by immunohistochemical staining. When two second-generation mice TK5-F1 and TK5-F2 were injected with GCV the pathogenic alterations in the liver were readily identified including the appearance of vaculation in the hepatocytes with inflammatory infiltration in the liver and diffuse proliferation of hepatocytes. In addition the blood test demonstrates a significant increase of serum alanine aminotransferase aspartate .