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| Content Provider | Springer Nature Link |
|---|---|
| Author | Fan, Jianglin Wang, Xiaofei Wu, Lihua Matsumoto, Shin Ich Liang, Jingyan Koike, Tomonari Ichikawa, Tomonaga Sun, Huijun Shikama, Hisataka Sasaguri, Yasuyuki Watanabe, Teruo |
| Copyright Year | 2004 |
| Abstract | Increased matrix metalloproteinase-12 (MMP-12) has been implicated in atherosclerosis and many other inflammatory processes. To define MMP-12 functions in vivo, we generated transgenic rabbits that expressed human (h) MMP-12 gene under the control of a macrophage-specific promoter, the human scavenger receptor promoter. Two transgenic founder rabbits were found to have hMMP-12 transgene integration by Southern blot analysis. hMMP-12 mRNA was expressed in peritoneal and alveolar macrophages, and in tissues enriched in macrophages in transgenic rabbits. High levels of hMMP-12 protein were detected in the conditioned media of cultured peritoneal and alveolar macrophages from transgenic rabbits. Zymography showed that hMMP-12 secreted from macrophages possessed enzymatic activity toward β-casein. To evaluate the expression of hMMP-12 in inflammatory sites, we used carrageenan-induced granulomas as an in vivo model for tissue macrophages and foam cells. Granuloma size in transgenic rabbits was significantly increased compared to that in control rabbits, and histological examination revealed that granulomas of transgenic rabbits were enriched in macrophages associated with increased hMMP-12 expression. We believe that this transgenic rabbit model with increased expression of hMMP-12 may become a useful model for further mechanistic studies of MMP-12 in inflammatory diseases and cancer invasion; it is also an ideal model for testing the in vivo action of MMP-12 inhibitors. |
| Starting Page | 261 |
| Ending Page | 269 |
| Page Count | 9 |
| File Format | |
| ISSN | 09628819 |
| Journal | Transgenic Research |
| Volume Number | 13 |
| Issue Number | 3 |
| e-ISSN | 15739368 |
| Language | English |
| Publisher | Kluwer Academic Publishers |
| Publisher Date | 2004-01-01 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Human Genetics Plant Sciences Plant Genetics & Genomics Animal Genetics and Genomics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science |
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