BALB/c-Zap70*W163C (SKG) Mouse

The Zeta-chain-associated protein kinase, encoded by the ZAP70 gene, is a member of the protein tyrosine kinase family and plays a crucial role in T cell development, activation, and lymphocyte activation. Upon stimulation of the T cell antigen receptor (TCR), the ZAP70 protein is phosphorylated on tyrosine residues and, together with Src family kinases Lck and Fyn, plays a role in the initial steps of TCR-mediated signal transduction ^[1]. ZAP70 plays a key role in T cell signal transduction and is vital for thymocyte development. Defects in the ZAP70 protein can lead to severe combined immunodeficiency (SCID), characterized by the selective absence of CD8-positive T cells. Moreover, the expression of ZAP70 in B cells is associated with developing chronic lymphocytic leukemia (CLL) ^[1-2].

SKG mice are a BALB/c background strain carrying the W163C mutation in the Zap70 gene. This mutation alters the binding of the ZAP70 protein to the CD3ζ chain based on the immunoreceptor tyrosine-based activation motif (ITAM), thereby reducing TCR signal transduction and allowing autoreactive T cells to escape negative selection in the thymus and migrate to the periphery ^[3]. Under natural conditions or upon administration of serum complement activators, mice develop chronic autoimmune arthritis mediated by Th17 cells ^[4-5]. Furthermore, studies have shown that stimulation through various methods such as β-glucan or mannan can induce the disease process of rheumatoid arthritis (RA) in SKG mice, resulting in symptoms of autoimmune diseases such as ankylosing spondylitis (AS), psoriasis-like skin inflammation, RA-associated interstitial lung disease (RA-ILD), and Crohn’s disease-like ileitis ^[6-9].

The BALB/c-Zap70*W163C (SKG) mouse (referred to as the SKG mouse) is an autoimmune disease research model constructed by Cyagen through gene editing technology to introduce the W163C mutation into the Zap70 gene of BALB/c mice. The phenotype of this model is similar to that of the classic SKG mouse ^[10]. Under SPF conditions, upon triggering innate immune activation (such as β-glucan induction), it can present a variety of autoimmune disease phenotypes. Therefore, this mouse can be used for research on autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis-like skin inflammation, RA-associated interstitial lung disease (RA-ILD), and Crohn’s disease-like ileitis, as well as T cell signal transduction.