A study of inflammatory bowel diseases using Smad2 conditional knockout mice.

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<Generation and analysis of T cell-specific Smad2 conditional knockout mice>Lck-Cre transgenic mice, which express Cre recombinase in a T cell-specific manner, was mated with Smad2^<+/-> mice and Lck-Cre Smad2^<+/-> mice were obtained. Then, Lck-Cre Smad2^<+/-> mice were mated with Smad2^<flox/flox> mice and Smad2^<flox/+>, Smad2^<flox/->, Lck-Cre Smad2^<flox/+> and Lck-Cre Smad2^<flox/-> mice were generated. Smad2 expression was down-regulated, but was not absent, in T cells from Lck-Cre Smad2^<flox/->. Spontaneous colitis was not observed in Lck-Cre Smad2^<flox/-> mice. In the dextran sulphate sodium induce colitis model and the oxazolone enema colitis model, there was not a significant difference in the level of colitis and expression of cytokines in colon between Smad2^<flox/+> and Lck-Cre Smad2^<flox/->.<Generation of macrophage/neutrophil-specific Smad2 conditional knockout mice>Smad2^<+/-> mice were mated with LysMcre mice, which express Cre recombinase in a macrophage/neutrophil-specific fashion, and LysMcre-Smad2^<flox/+> was obtained. Then, LysMcre-Smad2^<flox/+> was mated with Smad2^<flox/flox> mice and Smad2^<flox/+>, Smad2^<flox/flox>, LysMcre-Smad2^<flox/+> and LysMcre-Smad2^<flox/flox> mice were generated. In macrophages from LysMcre-Smad2^<flox/flox> mice, the expression of Smad2 was significantly decreased but was not absent. Spontaneous colitis was not observed in LysMcre-Smad2^<flox/flox> mice.<Conclusion>The evidence for the importance of Smad2 signaling in T cells or in macrophages and neutrophils for regulation of intestinal inflammation was not obtained.