Trex1-KO Mouse

The TREX1 gene encodes a 3'→5' DNA exonuclease, whose primary function is to degrade 3'-end mismatched single- and double-stranded DNA in the cytoplasm and nucleus. By clearing endogenous retrotransposable elements and DNA released from apoptotic cells, it prevents inappropriate activation of the innate immune system, thereby maintaining genomic stability and suppressing autoimmune responses ^[1]. TREX1 is widely expressed in various human tissues, with higher expression levels in lymphoid tissues, the thymus, and the spleen ^[2]. Mutations in TREX1 are associated with multiple autoimmune and inflammatory diseases, including Aicardi-Goutières syndrome (AGS), systemic lupus erythematosus (SLE), familial chilblain lupus (FCL), and retinal vasculopathy with cerebral leukodystrophy (RVCL). The pathogenesis of these diseases is often linked to chronic activation of the interferon signaling pathway due to defective DNA degradation ^[3].

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.