Matrix metalloproteinase 7 (MMP7) is a member of the matrix metalloproteinase family involved in extracellular matrix remodeling. MMP7 is predominantly expressed in epithelial cells and is secreted as an inactive zymogen. In activated alveolar epithelial cells, MMP7 cleaves osteopontin (OPN), thereby enhancing OPN activity and promoting a positive feedback loop that further upregulates and activates MMP7. This pro-fibrotic signaling cascade contributes to increased expression of extracellular matrix (ECM) proteins mediated by osteopontin. Multiple members of the MMP family participate in extracellular matrix remodeling during the development and progression of pulmonary fibrosis.

In MMP7 humanized mice (B-hMMP7), exons 1–6 of the mouse Mmp7 gene, which encode the full-length protein, as well as the 3′UTR, are replaced with the corresponding human MMP7 exons 1–6 and the human 3′UTR. The endogenous mouse promoter and 5′UTR are retained. Human MMP7 expression is therefore driven by the native mouse regulatory elements, while transcription and translation of the endogenous mouse Mmp7 gene are disrupted.

Validation studies demonstrate species-specific expression of MMP7 in this model. Mouse Mmp7 mRNA is detectable in wild-type mice but absent in homozygous MMP7 humanized mice (B-hMMP7), whereas human MMP7 mRNA is exclusively detectable in homozygous B-hMMP7 mice. These data support the use of this model for in vivo evaluation of human MMP7-targeted therapeutics. 

Key Advantages

• Species-specific target expression: Human MMP7 mRNA is exclusively detectable in MMP7 humanized mice (B-hMMP7), while mouse Mmp7 expression is restricted to wild-type controls.
• Endogenous regulatory control: Human MMP7 expression is driven by the retained mouse promoter and 5′UTR, enabling physiologically regulated expression in relevant tissues.
• Suitable for in vivo therapeutic evaluation: The model provides a genetically validated platform for assessing pharmacodynamic and efficacy effects of human MMP7-targeting agents.

Validation

• Human MMP7 mRNA expression: RT-PCR analysis confirms that human MMP7 mRNA is detectable only in MMP7 humanized mice (B-hMMP7), while mouse Mmp7 mRNA is detected only in wild-type mice.
• Disruption of endogenous mouse gene: Replacement of exons 1–6 results in loss of mouse Mmp7 transcription and translation in B-hMMP7 mice.

Applications

This model is suitable for pharmacodynamic and safety evaluation of MMP7-targeted therapeutics for IPF (idiopathic pulmonary fibrosis) and other related diseases.

In MMP7 humanized mice (B-hMMP7), exons 1–6 of the mouse Mmp7 gene, which encode the full-length protein, together with the mouse 3′UTR region, are replaced with human MMP7 exons 1–6 and the corresponding human 3′UTR. The mouse promoter and 5′UTR are retained as endogenous regulatory sequences. Human MMP7 expression is therefore driven by the endogenous mouse Mmp7 promoter, while transcription and translation of the mouse Mmp7 gene are disrupted.

Strain-specific analysis of MMP7 protein expression in serum was performed in wild-type C57BL/6 mice and homozygous MMP7 humanized mice (B-hMMP7) by ELISA. Serum was collected from wild-type C57BL/6 mice (+/+) (female, 8 weeks old, n=3) and homozygous MMP7 humanized mice (B-hMMP7, H/H, female, 8 weeks old, n=3). Protein expression levels of MMP7 were analyzed by ELISA using a Mouse MMP-7 ELISA Kit (Colorimetric, Novus Biologicals, NBP3-06895) and a Human Total MMP-7 Quantikine ELISA Kit (R&D Systems, DMP700). Mouse Mmp7 protein was detectable in wild-type C57BL/6 mice, whereas human MMP7 protein was exclusively detectable in homozygous MMP7 humanized mice (B-hMMP7). Values are expressed as mean ± SEM.

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

Q1: What are MMP7 humanized mice (B-hMMP7)?

MMP7 humanized mice (B-hMMP7) are genetically engineered mice in which exons 1–6 and the 3’UTR of the mouse Mmp7 gene are replaced by the corresponding human MMP7 sequences. This enables physiological expression of human MMP7 under control of the endogenous mouse promoter while disrupting native mouse Mmp7 transcription and translation.

Q2: How is human MMP7 expression validated in MMP7 humanized mice (B-hMMP7)?

Species-specific RT-qPCR and ELISA analyses demonstrate that mouse Mmp7 mRNA and protein are detectable only in wild-type mice, whereas human MMP7 mRNA and protein are exclusively detectable in homozygous MMP7 humanized mice (B-hMMP7).

Q3: What are the main applications of MMP7 humanized mice (B-hMMP7)?

MMP7 humanized mice (B-hMMP7) are used for pharmacodynamic and safety evaluation in idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases, supporting in vivo assessment of MMP7-targeted therapeutics.