• Integrin α4β7 is composed of a 150 kD (α4 or CD49d) and a 130 kD (β7) heterodimer, also known as CD49d/β7 or LPAM-1. Belonging to the Ig superfamily, it is found on the majority of peripheral lymphocytes and subsets of thymocytes and bone marrow cells (including mast cell progenitors). Integrin α4β7 binds its ligands, VCAM-1 (CD106), MAdCAM-1 and fibronectin, and plays an important role in lymphocytes adhesion and the direction of migration of blood lymphocytes to the intestine and associated lymphoid tissues.
• The IL-7 receptor alpha chain (IL-7Ra) and the common gamma chain (γc) serve as the components of the IL-7 receptor, undergoing dimerization upon binding with the IL-7 ligand. IL-7 and its receptor IL-7R are crucial for the normal development, differentiation, and survival of T cells and B cells. Abnormal IL-7/IL-7R signaling is believed to be associated with the pathogenesis of various autoimmune or inflammatory diseases.
• The genome of the mouse Itga4 gene encoding the extracellular domain was replaced with human ITGA4 counterpart in B-hα4β7/hIL7R mice. The genome of the mouse Itgb7 gene encoding the extracellular domain was replaced with human ITGB7 counterpart in B-hα4β7/hIL7R mice. The genome of the mouse Il7r gene encoding the extracellular domain was replaced with human IL7R counterpart in B-hα4β7/hIL7R mice.
• Human ITGA4, ITGB7, IL7R protein were exclusively detectable in homozygous B-hα4β7/hIL7R mice.
• This product is used for the evaluation of the pharmacodynamics and safety of anti-human α4β7/IL7R antibodies in autoimmune diseases such as inflammatory bowel disease.

Gene targeting strategy for B-hα4β7/hIL7R mice.

The exons 2-27 of mouse Itga4 gene that encode the extracellular domain were replaced by human counterparts in B-hα4β7/hIL7R mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were retained. The human ITGA4 expression was driven by endogenous mouse Itga4 promoter, while mouse Itga4 gene transcription and translation will be disrupted.

The exons 2-14 of mouse Itgb7 gene that encode the extracellular domain were replaced by human counterparts in B-hα4β7/hIL7R mice. The promoter, 5’UTR and 3’UTR region of the mouse gene were retained. The human ITGB7 expression was driven by endogenous mouse Itgb7 promoter, while mouse Itgb7 gene transcription and translation will be disrupted.

The exons 1-6 of mouse Il7r gene that encode the extracellular region were replaced by human IL7R exons 1-6 in B-hα4β7/hIL7R mice.

Note: B-hα4β7/hIL7R mice were obtained by mating B-hα4β7 mice (111913) and B-hIL7R mice (110082).

Strain specific ITGA4 and ITGB7 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hα4β7/hIL7R mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hα4β7/hIL7R mice (H/H;H/H;H/H). Protein expression was analyzed with anti-mouse ITGA4 antibody (Biolegend, 103705), anti-mouse LPAM-1/α4β7 antibody (Biolegend, 120607), anti-human ITGA4 antibody (Biolegend, 304307) anti-human ITGB7 antibody (Invitrogen, MA5-23541) by flow cytometry. Mouse ITGA4 and ITGB7 were only detectable in wild-type C57BL/6JNifdc mice. Human ITGA4 and ITGB7 were exclusively detectable in homozygous B-hα4β7/hIL7R mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific ITGA4 and ITGB7 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hα4β7/hIL7R mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hα4β7/hIL7R mice (H/H;H/H;H/H). Protein expression was analyzed with anti-mouse ITGA4 antibody (Biolegend, 103705), anti-mouse LPAM-1/α4β7 antibody (Biolegend, 120607), anti-human ITGA4 antibody (Biolegend, 304307) anti-human ITGB7 antibody (Invitrogen, MA5-23541) by flow cytometry. Mouse ITGA4 and ITGB7 were only detectable in wild-type C57BL/6JNifdc mice. Human ITGA4 and ITGB7 were exclusively detectable in homozygous B-hα4β7/hIL7R mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific ITGA4 and ITGB7 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hα4β7/hIL7R mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hα4β7/hIL7R mice (H/H;H/H;H/H). Protein expression was analyzed with anti-mouse ITGA4 antibody (Biolegend, 103705), anti-mouse LPAM-1/α4β7 antibody (Biolegend, 120607), anti-human ITGA4 antibody (Biolegend, 304307) anti-human ITGB7 antibody (Invitrogen, MA5-23541) by flow cytometry. Mouse ITGA4 and ITGB7 were only detectable in wild-type C57BL/6JNifdc mice. Human ITGA4 and ITGB7 were exclusively detectable in homozygous B-hα4β7/hIL7R mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific ITGA4 and ITGB7 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hα4β7/hIL7R mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hα4β7/hIL7R mice (H/H;H/H;H/H). Protein expression was analyzed with anti-mouse ITGA4 antibody (Biolegend, 103705), anti-mouse LPAM-1/α4β7 antibody (Biolegend, 120607), anti-human ITGA4 antibody (Biolegend, 304307) anti-human ITGB7 antibody (Invitrogen, MA5-23541) by flow cytometry. Mouse ITGA4 and ITGB7 were only detectable in wild-type C57BL/6JNifdc mice. Human ITGA4 and ITGB7 were exclusively detectable in homozygous B-hα4β7/hIL7R mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific ITGA4 and ITGB7 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hα4β7/hIL7R mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hα4β7/hIL7R mice (H/H;H/H;H/H). Protein expression was analyzed with anti-mouse ITGA4 antibody (Biolegend, 103705), anti-mouse LPAM-1/α4β7 antibody (Biolegend, 120607), anti-human ITGA4 antibody (Biolegend, 304307) anti-human ITGB7 antibody (Invitrogen, MA5-23541) by flow cytometry. Mouse ITGA4 and ITGB7 were only detectable in wild-type C57BL/6JNifdc mice. Human ITGA4 and ITGB7 were exclusively detectable in homozygous B-hα4β7/hIL7R mice, but not in wild-type C57BL/6JNifdc mice.

Strain specific IL7R expression analysis in homozygous B-hα4β7/hIL7R mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hα4β7/hIL7R mice (H/H;H/H;H/H), protein expression was analyzed by flow cytometry with species-specific anti-mouse IL7R antibody (Biolegend, 135011) and anti-human IL7R antibody (Biolegend, 351303). Mouse IL7R was detectable in wild-type C57BL/6JNifdc mice. Human IL7R was detectable in homozygous B-hα4β7/hIL7R mice.