Research Project
Grant-in-Aid for Scientific Research (C)
Mitogen-activated protein kinases(MAPKs) are activated in response to various extracellular stimuli. Extracellular signal-regulated kinase(ERK), a MAPK family, has been implicated in T cell differentiation, proliferation and cytokine production. The ERK family consists of two members, ERK1 and ERK2. Recently, defective thymocyte maturation has been reported in ERK1-deficient mice. However, roles of ERK2 in the regulation of immune system remain to be determined. Here we show that the targeted disruption of the mouse ERK2 gene results in embryonic lethality by E11.5 and severe abnormality of the placenta. In these animals, the labyrinthine layer of the placenta is very thin and few fetal blood vessels are observed. ERK2 mutants can be rescued by the transgenic expression of ERK2, demonstrating that these abnormalities are caused by ERK2-deficiency. Although ERK2-deficient fetuses are much smaller than wild-type littermates, this seems to be secondary to malfunction of the placenta. When the placental defect is rescued by tetraploid-aggregation, ERK2-deficient fetuses grow as well as littermate controls.As described above, ERK2-deficient mice were embryonic lethal due to placental defect. So we generated ERK2 conditional knockout mice to study the physiological role of ERK2 in the immune system. We generated T cell-specific ERK2-deficient mice using LCK-Cre transgenic mice. These mice were viable and more than 95% ERK2 gene was disrupted in the thymocytes. ERK2 protein was undetectable in the thymocytes. In the thymus, CD3^<high> CD4^+ or CD8^+ mature T cells were significantly decreased. Thus, ERK2 is essential for development of T cells.
All 2004 2003 Other
All Journal Article (13 results) Publications (5 results)
Endocrinology. 15
Pages: 2006-2013
Life Sci 75
Pages: 2193-2201
Endocrinology. 145
Life Sci. 75
Genes to Cells. 8
Pages: 847-856
J Cell Biol. 160
Pages: 12-5135
J.Biol.Chem. 278
Pages: 7167-7179
Diabetes. 52
Pages: 2720-2730
Genes to Cells 8
Pages: 125-135
