B6-hITGA4 Mice

Catalog Number: C001635

Strain Name: C57BL/6NCya-Itga4em1(hITGA4)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Heterozygote x Heterozygote

 

Strain Description

The ITGA4 gene encodes the integrin α4 subunit, which heterodimerizes with the β7 subunit to form α4β7, a transmembrane protein of the integrin family [1]. α4β7 is prominently expressed in immune tissues, including lymph nodes, bone marrow, spleen, and blood, as well as in diverse immune cell populations, such as T lymphocytes, B lymphocytes, monocytes, granulocytes, and natural killer cells [1]. Functionally, α4β7 mediates cell adhesion and migration, critically regulating immune cell trafficking and inflammatory processes. Specifically, α4β7 facilitates lymphocyte migration to sites of inflammation and intestinal lymphoid tissues through interactions with vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) [2]. Notably, ITGA4 has been implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, and multiple sclerosis [2-4]. Consequently, the targeting of α4β7 has emerged as a key therapeutic strategy for inflammatory and autoimmune disorders.

The B6-hITGA4 mouse is a humanized model constructed using gene editing technology, where a portion of the mouse Itga4 gene was replaced with "ITGA4 chimera CDS-WPRE-BGH pA" cassette. The murine ITGA4 signal peptide (aa.1~40) was preserved. This model can be used for studying the pathological mechanisms and therapeutic approaches of inflammatory and autoimmune diseases, and for the development of ITGA4-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hITGA4 mice. The region from aa.41 in exon 1 to partial intron 1 of mouse Itga4 was replaced with "ITGA4 chimera CDS-WPRE-BGH pA" cassette. The murine signal peptide (aa.1~40) was preserved.

 

Application

  • ITGA4-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of inflammatory and autoimmune diseases.

 

References
[1]Slack RJ, Macdonald SJF, Roper JA, Jenkins RG, Hatley RJD. Emerging therapeutic opportunities for integrin inhibitors. Nat Rev Drug Discov. 2022 Jan;21(1):60-78.
[2]Gros B, Kaplan GG. Ulcerative Colitis in Adults: A Review. JAMA. 2023 Sep 12;330(10):951-965.
[3]Cushing K, Higgins PDR. Management of Crohn Disease: A Review. JAMA. 2021 Jan 5;325(1):69-80.
[4]Gubatan J, Keyashian K, Rubin SJS, Wang J, Buckman CA, Sinha S. Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives. Clin Exp Gastroenterol. 2021;14:333-342