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L. W. Reneker, M. L. Robinson, M. Ogata, H. Sanjo, G. Pages; The Role of ERK Mitogen-Activated Protein Kinase (MAPK) in Lens Development. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1119.
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Growth factors have been implicated as regulators to control lens cell proliferation, differentiation and survival during normal development. Our previous studies have shown that the Ras-ERK pathway downstream of the receptor tyrosine kinases (RTKs) plays an essential role in lens cell proliferation and lens growth. The purpose of this study is to further investigate the role of ERK MAPKs in lens development.
Mice that carry ERK1 null or ERK2-flox conditional allele were used in this study. Conditional deletion of ERK2 in the lens was accomplished with two Cre-expressing transgenic mouse lines: MLR10 and MLR39. In MLR10 mice, Cre expresses in both lens epithelial and fiber cells whereas in MLR39 mice, Cre expression is restricted to the lens fiber cells. Lenses from mutant and wild-type mice were analyzed by PCR and histology.
The lens in the ERK1 null mice looks normal. Deletion of ERK2 mediated by Cre in either MLR10 or MLR39 mice did not result in any gross morphological abnormalities in the lens. PCR of lens DNA isolated from the MLR39-ERK2flox/flox mice showed the presence of both deleted and non-deleted ERK2 allele. This result is in agreement with the finding that Cre is expressed only in the lens fiber cells in MLR39 mice. PCR of lens DNA from the MLR10-ERK2flox/flox mice has not been examined at this point. When ERK2-deficient embryos were rescued from placental defects by tetraploid aggregation, the mutant embryos grow as well as the wild-type littermates at least until embrynoc day 13.5 (E13.5) with no visible eye abnormalities.
Absence of ERK1 or ERK2 in the lens does not result in any visible lens defects, suggesting that normal lens development does not require the presence of both ERK MAPKs. ERK1 and ERK2 may play a redundant role in regulation of lens cell proliferation and differentiation during development. Further studies of deleting both ERK1 and ERK2 in the lens will determine the essential role of ERK in lens development.
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