The Trex1 KO mouse is a knockout (KO) model in which the protein-coding sequence of the Trex1 gene (homologous to the human TREX1 gene) has been deleted via gene-editing technology. Preliminary validation data indicate that homozygous Trex1 KO mice typically die of myocarditis at 3–4 months of age. Although some 3-month-old homozygotes are fertile, most exhibit premature weakness and are unable to breed. This model can be used to study the pathogenic mechanisms of diseases such as Aicardi-Goutières syndrome (AGS), systemic lupus erythematosus (SLE), familial chilblain lupus (FCL), and retinal vasculopathy with cerebral leukodystrophy (RVCL), and to provide a basis for developing related therapeutic strategies.