GENE THERAPY FOR HEPATIC CIRRHOSIS AND HEPATOMA IN LEC RAT BY INTRODUCING HUMAN ATP7B cDNA / 解剖学报

ABSTRACT

Objective To investigate the possibility of affecting transgenic therapy for the hepatic cirrhosis and hepatoma in Wilson disease by human ATP7B cDNA. Methods The 7.1*!kb transgene consisting of human ATP7B cDNA and chiken ?-actin promoter was introduced into the LEC rats which is an animal model of Wilson disease by microinjection.The plasma AST and ALT activities in transgenic rats were measured continuously from weeks 17 to 30 using non-transgenic and LEA rats as controls.The histological and histochemistry changes of liver in the transgenic rats at 30 and 60 weeks of age were examined. Results The plasma AST and ALT activities in transgenic rats were kept at the relatvie lower levels from 17 to 60 weeks of age, as compared to the age-matched non-transgenic rats.By the age of 60 weeks,none of the transgenic males developed cholangiofibrosis or hepatoma,whereas all of the non-transgenic rasts had severe cholangiofibrosis at the age of 30 weeks and one male rat had hepatoma at 60 weeks.The transgenic rats were phenotypically normal,and the survival rate was 95.7%.In addition,the distribution and the numbers of the granules of stained copper in the hepatocytes of the transgenic rats did not show any significant difference between 30 and 60 weeks.Conclusion The human ATP7B successfully delayed the onset of hepatic cirrhosis,and suppressed the development of hepatoma in the LEC rats by gene transfer.The hepatic cirrhosis and hepatoma in Wilson disease may be not directly related to the copper accumulation.