Construction of Transgenic Fah-/-Liver Injury Mouse Model
Objective To establish a transgenic Fah-/-liver injury mouse model and explore the mechanism of liver injury.Method SPF C57BL/6J wild-type mice were selected as WT group.According to the result of gene identification,24 Fah-/-homozygous mice aged 6-8 weeks were selected and divided into the NTBC drinking water group,the NTBC drinking water stop group for one week,and the NTBC drinking water stop group for two weeks.The weight was weighed,blood was collected,serum was isolated,liver function biochemical indexes were tested,and the animals were sacrificed.The expression of Fah protease and Fah protein were detected by immunohistochemistry and Western blot.Result After gene identification,24 Fah-/-homozygous mice were successfully bred.The result of subsequent study on the mechanism of liver injury showed that ALT,AST and TBIL of liver function in the one-week and two-week NTBC cessation groups were significantly increased compared with those in the normal NTBC group,while ALB was significantly decreased,with statistical significance.Pathological HE staining result of liver tissue showed that the structure of liver tissue in WT group and normal NTBC group was normal,while different degrees of lesions such as hepatocyte hypertrophy,necrosis and inflammatory cell infiltration were observed in NTBC group.The longer the time of NTBC cessation,the more serious the degree of liver injury.The result of liver immunohistochemistry showed that the expression of Fah protease in WT group was strongly positive,the expression of Fah protease in normal NTBC group was negative,and the expression of Fah protease in hepatocytes of the one-week and two-week NTBC stop groups was weakly positive.The expression of Fah protein by Western blot was consistent with that by immunohistochemistry.Conclusion The Fah-/-mouse model was successfully established and the mechanism of liver injury was studied,so as to provide experimental data reference for subsequent studies.