| First Author | Li G | Year | 2016 |
| Journal | Biol Open | Volume | 5 |
| Issue | 4 | Pages | 418-23 |
| PubMed ID | 26977076 | Mgi Jnum | J:231579 |
| Mgi Id | MGI:5771912 | Doi | 10.1242/bio.016279 |
| Citation | Li G, et al. (2016) Establishment and evaluation of a transgenic mouse model of arthritis induced by overexpressing human tumor necrosis factor alpha. Biol Open 5(4):418-23 |
| abstractText | Tumor necrosis factor alpha (TNFalpha) plays a key role in the pathogenesis of rheumatoid arthritis (RA). Blockade of TNFalpha by monoclonal antibody has been widely used for the therapy of RA since the 1990s; however, its mechanism of efficacy, and potential safety concerns of the treatment are still not fully understood. This study sought to establish a transgenic arthritic mouse model by overexpressing human TNFalpha (hTNFalpha) and to apply this model as a means to evaluate therapeutic consequences of TNFalpha inhibitors. The transgenic mouse line (TgTC) with FVB background was generated by incorporating 3'-modifiedhTNFalphagene sequences. A progressively erosive polyarthritis developed in the TgTC mice, with many characteristics observed in human rheumatoid arthritis, including polyarticular swelling, impairment of movement, synovial hyperplasia, and cartilage and bone erosion. Gene expression analysis demonstrated that hTNFalpha is not only expressed in hyperplastic synovial membrane, but also in tissues without lesions, including brain, lung and kidney. Treatment of the TgTC mice with anti-hTNFalpha monoclonal antibodies (mAb) significantly decreased the level of hTNFalpha in the diseased joint and effectively prevented development of arthritis in a dose-dependent response fashion. Our results indicated that the TgTC mice represent a genetic model which can be used to comprehensively investigate the pathogenesis and therapeutics of TNFalpha-related diseases. |
