- Response to Comment on "Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis"
- Molecular Medicine
- Volume | Issue number
- 17 | 11-12
- Pages (from-to)
- Document type
- Faculty of Medicine (AMC-UvA)
In our recent work we utilized genetically modified mice to investigate the role of tissue factor (TF) in experimental colitis. We present evidence suggesting TF plays a detrimental role in this disease via signal transduction dependent KC production in colon epithelial cells, which provokes granulocyte influx leading to subsequent inflammation and organ damage. We agree with Gambone et al. that experiments using genetically modified mice should ideally be performed with littermate controls. Unfortunately, intercrosses of 50% TF mice are problematic and employing this strategy resulted in insufficient TFlow (1%) mice within a similar age category as littermate wildtype controls. Consequently, we opted for an experimental set-up in which littermate 1% and 50% TF mice were compared with non-littermate C57Bl/6 wildtypes. The 1 and 50% TF mice had been backcrossed for 6 generations with C57BL/6 mice and are thus largely on a C57Bl/6 genetic background (1). However, we performed a control experiment to exclude potential strain differences biasing our results. To this end, wildtype mice obtained from an intercross of 50% TF mice were compared with non-littermate wildtype C57Bl/6 mice in the DSS-induced experimental colitis model as described in our paper (2). In this particular experiment we did not observe differences between the groups with respect to body weight loss, increase in colon weight, reduction in colon length and disease severity score. Unfortunately however, disease symptoms were rather mild and somewhat variable (perhaps resulting from a new batch of DSS). After careful consideration we decided not to include these data in the published manuscript. Despite the limitations of this control experiment, we are confident the differences reported in our paper are indeed due to changes in TF levels and not due to strain differences
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