Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), also known as cluster of differentiation 152 (CD152), is an immunoglobulin superfamily protein encoded by the CTLA4 gene. CTLA4 is expressed by activated T cells and delivers inhibitory signals to T cells ^[1]. The structure of the CTLA4 protein contains a V-domain, a transmembrane domain, and a cytoplasmic tail. Different splicing patterns of CTLA4 pre-mRNA lead to the appearance of different isoforms, among which the membrane-bound isoform is linked by disulfide bonds to form homodimers, while the soluble isoform exists as a monomer. CTLA4 is homologous to CD28, which delivers T-cell activation signals. Both molecules compete for binding to the natural B7 family ligands B7-1 and B7-2 on antigen-presenting cells, but CTLA4 has a much higher affinity for binding to B7-1 and B7-2 than CD28. This results in the inhibition of T cell activation, allowing tumor cells to escape from T cell attack ^[2]. The gene is closely associated with the occurrence or progression of insulin-dependent diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated ophthalmopathy, and other autoimmune diseases ^[3].

CTLA4 is a membrane protein, with its extracellular domain serving as the receptor/ligand binding region and its intracellular domain responsible for signal transduction ^[4]. This strain was generated by gene editing to replace the extracellular domain of Ctla4 in mice with the humanized version, resulting in a model that expresses the extracellular domain of human CTLA4 and the intracellular domain of mouse CTLA4. This model can be used for the research of the development and screening of CTLA4-related inhibitors or antibody drugs, the evaluation of pharmacodynamics and safety, the evaluation of tumor immunotherapy, and the mechanisms of the immune system.