• Background: MMP7 is mostly expressed in epithelial cells, which is secreted as a zymogen. In activated alveolar epithelial cells, MMP-7 cuts osteopontin (OPN) and enhances its function, thereby upregulating and activating MMP-7. In this pro-fibrotic effect, osteopontin upregulates the expression of ECM (extracellular matrix) proteins. Various MMPs are involved in the process of pulmonary fibrosis.
• Targeting strategy: The exons 1-6 of mouse Mmp7 gene that encode full length protein and 3’UTR regions are replaced by human MMP7 exons 1-6 as well as 3’UTR regions in B-hMMP7 mice. The promoter and 5’UTR of the mouse gene are retained as mouse sequence and 3’UTR is replaced with human sequence.
• Validation: Mouse MMP7 protein was detectable in wild-type C57BL/6 mice. Human MMP7 protein was exclusively detectable in homozygous B-hMMP7 mice. Mouse Mmp7 was only detected in wild-type C57BL/6 mice and human MMP7 was exclusively detected in homozygous B-hMMP7 mice. CT values for both mouse Mmp7 and human MMP7 were approximately 31 (total cycle: 40).
• Application: This product is used for pharmacodynamics and safety evaluation of IPF (idiopathic pulmonary fibrosis) and other diseases

Gene targeting strategy for B-hMMP7 mice. The exons 1-6 of mouse Mmp7 gene that encode full length protein and 3’UTR regions are replaced by human MMP7 exons 1-6 as well as 3’UTR regions in B-hMMP7 mice. The promoter and 5’UTR of the mouse gene are retained as mouse sequence and 3’UTR is replaced with human sequence. Human MMP7 expression is driven by endogenous mouse Mmp7 promoter, while mouse Mmp7 gene transcription and translation will be disrupted.

Strain specific MMP7 expression analysis in wild-type C57BL/6 mice and homozygous humanized B-hMMP7 mice by ELISA. Serum was collected from wild-type C57BL/6 mice (+/+) (Female, 8-weeks-old, n=3) and homozygous B-hMMP7 mice (H/H) (Female, 8-weeks-old, n=3). Protein expression level of MMP7 was analyzed by ELISA (Mouse MMP-7 ELISA Kit (Colorimetric), Novus Biologicals, NBP3-06895; Human Total MMP-7 Quantikine ELISA Kit, R&D, DMP700). Mouse MMP7 was detectable in wild-type C57BL/6 mice. Human MMP7 was exclusively detectable in homozygous B-hMMP7 mice. Values are expressed as mean ± SEM.

Strain specific analysis of MMP7 gene expression in wild-type C57BL/6 mice and hMMP7 mice by RT-qPCR. Lung RNA were isolated from wild-type C57BL/6 mice (+/+) (n=3, male, 9-week-old) and homozygous B-hMMP7 mice (H/H) (n=3, male, 9-week-old) , then 40 ng total RNA was used for cDNA library synthesis by reverse transcription, followed by real-time quantitative PCR with MMP7 primers. Mouse Mmp7 was only detected in wild-type C57BL/6 mice and human MMP7 was exclusively detected in homozygous B-hMMP7 mice. CT values of both mouse Mmp7 and human MMP7 were approximately 31 (total cycle: 40). Values are expressed as mean ± SEM.