hITGA4 Mouse

The ITGA4 gene encodes the integrin α4 subunit, which associates with the integrin β7 subunit (ITGB7) to form the heterodimeric transmembrane protein α4β7, an important member of the integrin family ^[1,2]. The α4β7 integrin is expressed in a variety of cells and tissues and is highly expressed in immune tissues such as lymph nodes, bone marrow, spleen, and blood, as well as in multiple immune cell types including T lymphocytes, B lymphocytes, monocytes, granulocytes, and natural killer cells ^[3]. Its primary functions are to mediate cell adhesion and migration, thereby regulating the tissue homing of immune cells and inflammatory responses. By binding to vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1), α4β7 promotes the migration of lymphocytes to inflamed tissues and gut-associated lymphoid tissues ^[1,2,4]. Studies have shown that the ITGA4 gene is closely linked to the pathogenesis and progression of multiple diseases, including autoimmune disorders such as inflammatory bowel disease (IBD), Crohn’s disease, ulcerative colitis, and multiple sclerosis (MS) ^[1,2,5]. Furthermore, high expression of ITGA4 in gastric cancer is associated with poor prognosis, cell proliferation and migration, as well as immune infiltration; its downregulation inhibits migration and promotes apoptosis ^[3]. Given the critical role of α4β7 integrin in inflammation and immune responses, targeting α4β7 has become an important research direction for the treatment of inflammatory and autoimmune diseases.

The hITGA4 mouse is a humanized model generated by gene-editing technology. The coding sequences of exon 2 plus partial intron 2 of mouse Itga4 were replaced with Chimeric ITGA4 CDS-WPRE-BGH pA cassette. The murine signal peptide was retained. hITGA4 mice can be used to investigate the pathological mechanisms and therapeutic strategies of inflammatory and autoimmune diseases, as well as for the screening, development, and preclinical efficacy and safety evaluation of ITGA4-targeted drugs.