Description

• ITGA11 is  a 160 kDa member of the integrin alpha chain family of molecules. Integrin α11, also known as type I collagen receptor, is a single-pass type I transmembrane protein that mediates cell-matrix adhesion and is part of the family of integrins that play a pivotal role in regulation processes of cell proliferation, differentiation, migration, tumor invasion, and metastasis. Integrin α11 is highly expressed in embryonic fibroblasts and myofibroblasts and to varying degrees in the cytoplasm of most human tissues. As a receptor for type I collagen, which is found in fibrotic tissue of the liver, lung, and kidney, integrin α11 colocalizes with α-smooth muscle actin. Type I collagen is the most abundant form in the body, indicating a role for targeting integrin α11 in the therapeutic intervention of fibrotic disease.
• The exons 2~29 of mouse Itga11 gene that encode the extracellular domain were replaced by human ITGA11 exons 2~29 in B-hITGA11 mice. The genomic region of mouse Itga11 gene that encodes signal peptide, transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The ITGA11 expression was driven by endogenous mouse Itga11 promoter, while mouse Itga11 gene transcription and translation will be disrupted.
• Mouse Itga11 mRNA was only detectable in wild-type mice. Human ITGA11 mRNA was exclusively detectable in homozygous B-hITGA11 mice but not in wild-type mice.
• hITGA11 was expressed in uterus, skin, liver, lung, kidney and heart of humanized mice, and was less expressed in liver of humanized mice.

Targeting strategy

Gene targeting strategy for B-hITGA11 mice. The exons 2~29 of mouse Itga11 gene that encode the extracellular domain were replaced by human ITGA11 exons 2~29 in B-hITGA11 mice. The genomic region of mouse Itga11 gene that encodes signal peptide, transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The ITGA11 expression was driven by endogenous mouse Itga11 promoter, while mouse Itga11 gene transcription and translation will be disrupted.

mRNA expression analysis

Strain specific analysis of ITGA11 mRNA expression in wild-type C57BL/6 mice and B-hITGA11 mice by RT-PCR. Kidney RNA were isolated from wild-type C57BL/6 mice (+/+) and homozygous B-hITGA11 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human ITGA11 primers. Mouse Itga11 mRNA was only detectable in wild-type mice. Human ITGA11 mRNA was exclusively detectable in homozygous B-hITGA11 mice but not in wild-type mice.

Protein expression analysis

Western blot analysis of ITGA11 protein expression in homozygous B-hITGA11 mice. Various tissue lysates were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hITGA11 mice (H/H), and then analyzed by western blot with species-specific anti-ITGA11 antibody (CST, 37815). 40 μg total proteins were loaded for western blotting analysis. hITGA11 was expressed in uterus, skin, liver, lung, kidney and heart of humanized mice, and was less expressed in liver of humanized mice.