Abstract: Objective: Previous studies have demonstrated that LRP16 is an estrogen-responsive gene,the expression level of which is tightly linked with proliferation and invasive growth of human breast cancer cells.To further explore the physiological function of LRP16,here,we transfected LRP16 targeting vector pBΔ16 into ES cells and screened the ES clone with inactive LRP16 gene.Methods: ES cells were screened with G418 and the homologously recombinant clone was identified from 100 clones by southern blot analysis.Results: There was an ES clone with targeting sequence homolougously inserted.Conclusion: A homologous recombinant was obtained.The study lays the foundations of preparing mouse models of LRP16 knockout.