Tbx21-LSL-P2A-DTR Mouse

Tbx21 (T-box transcription factor 21) gene encodes the T-box transcription factor T-bet, an important transcription factor that regulates immune cell differentiation and function. T-bet mainly promotes the differentiation of CD4⁺ helper T cells into Th1 cells, activates the expression of related genes such as interferon γ (IFN-γ), and inhibits the Th2 cell differentiation program. In addition, T-bet also participates in the functional regulation of CD8⁺ cytotoxic T cells, some natural killer cells, and regulatory T cells. Tbx21 deficiency can lead to impaired Th1 immune responses and alter the body's responses to infection and inflammation, indicating that this gene plays an important role in cellular immune regulation and maintenance of immune homeostasis ^[1-2].

The Tbx21-LSL-P2A-DTR mouse model is constructed by gene editing technology, in which the stop codon of the mouse Tbx21 gene is replaced with the cassette "loxP-AA-6xSV40 pA-loxP-TG-P2A-DTR". In the absence of Cre recombination, the T-bet transcript continues translation into the loxP sequence, adding a stretch of amino acids encoded by loxP to the C-terminus of the protein; the artificially introduced “AA” creates a new stop codon, while the 6×SV40 polyA serves as a transcriptional terminator that blocks downstream expression. After Cre-mediated excision of the LSL (loxP-stop-loxP) cassette, the remaining sequence is expressed under the control of the endogenous Tbx21 regulatory elements. DTR is the diphtheria toxin receptor; administration of diphtheria toxin (DT) enables selective ablation of cells expressing this receptor. This model can be used to study the function of Tbx21-positive cells, including senescence-associated cells and tumor cells.