B6-hα4β7 Mice

Catalog Number: C001689

Strain Name: C57BL/6NCya-Itga4em1(hITGA4)Itgb7em1(hITGB7)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Heterozygote B6-hITGA4 mice x Heterozygote B6-hITGB7 mice

 

Strain Description

The ITGA4 gene encodes the integrin α4 subunit, which pairs with the integrin β7 subunit, encoded by the ITGB7 gene, to form the heterodimeric transmembrane protein α4β7, a key member of the integrin protein 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 and ITGB7 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.

B6-hα4β7 mice are ITGA4 and ITGB7 double humanized mouse models obtained by mating ITGA4 humanized mouse models (Catalog No. C001635) with ITGB7 humanized mouse models (Catalog No. C001637). B6-hα4β7 mice express human ITGA4 and ITGB7 genomic sequences under the control of mouse promoters. This model is capable of reproducing human α4β7 and is a valuable tool for studying immune-related diseases. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting α4β7.

 

Strain Strategy

  • Gene editing strategy of B6-hITGB7 mice. The mouse Itgb7 endogenous extracellular domain (aa.20~724) was replaced with the human ITGB7 extracellular domain (aa.20~723). The murine signal peptide (aa.1~19) was preserved.



  • 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

  • α4β7-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