Objective:To construct lecithin - cholesterolacyl transferase(LCAT)knock -in mice by CRISPR/Cas9 - mediated gene editing and to obtain liver-specific overexpression of Lcat mice by mating with liver-specific Cre-expressing transgenic mice. Providing an animal model for the study of the mechanism of the Lcat gene in the development of liver-related metabolic diseases. Methods:Lcat knock -in mice were constructed by CRISPR/Cas9 technology;Liver - specific Cre- expressing transgenic mice were mated with Lcat knock -in mice to obtain liver -specific overexpressing Lcat mice;Genotyping mice by PCR;Quantitative real -time PCR(qPCR)and Western blot(WB)techniques were used to verify the expression of Lcat gene in C57BL/6 mice. Results:The PCR results showed that the liver-specific overexpression of Lcat gene in mice was successfully constructed;the qPCR results showed that the Lcat gene was specifically highly expressed in the liver,and the liver of knock -in mice showed higher Lcat expression;the WB results showed that LCAT protein was more highly expressed in the liver of liver-specific Lcat knock-in mice. Conclusion:Liver-specific overexpression of Lcat gene mice were successfully constructed,providing a platform for exploring the function of the Lcat gene at animal level in liver-related metabolic diseases and the associated pathogenesis.