2005 Fiscal Year Final Research Report Summary
A study of inflammatory bowel diseases using Smad2 conditional knockout mice.
| Project/Area Number |
16590603
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | KYUSHU UNIVERSITY |
|---|
Principal Investigator |
NAKAMURA Kazuhiko Kyushu University, Graduate School of Medical Sciences, Research associate, 大学院・医学研究院, 助手 (00274449)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NOMURA Masatoshi Kyushu University, University Hospital, Research associate, 大学病院, 助手 (30315080)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | Inflammatory bowel diseases / Smad2 / T cell / macrophage / neutrophil |
|---|
| Research Abstract |
<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.
|
Research Products
(12 results)
