Purchase this article with an account.
Xiaohua Gong, Xin Wang, Jiahuai Han, Ingrid Niesman, Qingling Huang, Joseph Horwitz; Development of Cataractous Macrophthalmia in Mice Expressing an Active MEK1 in the Lens. Invest. Ophthalmol. Vis. Sci. 2001;42(3):539-548.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. To characterize the extracellular signal-regulated kinase (ERK) pathway in
the lens and to try to understand how this pathway contributes to lens
function and cataractogenesis.
methods. The members of the ERK pathway in the lens were examined by Western
blotting, immunohistochemical staining, and kinase assay. A
gain-of-function approach was used to perturb the ERK pathway in the
lenses of transgenic mice via expression of a constitutively active
mutant of the mitogen-activated protein kinase kinase 1 (MEK1(E)), the
direct upstream kinase of the ERK1 and ERK2 kinases, under theα
results. The presence of an active ERK pathway was found in lens epithelial
cells and in differentiating fibers. Transgenic mice that expressed
MEK1(E) developed postnatal cataracts as well as macrophthalmia.
Distinct morphologic alterations, such as lens enlargement, swelling
fiber cells, enlarged extracellular space, and vacuole formation, were
observed in the lenses of these transgenic mice. A significant increase
in the glucose transporter 1 (GLUT1) level, as well as in the glucose
level, was detected in the lens.
conclusions. The MAP kinase pathway is involved in the regulation of glucose
metabolism and balance in the mouse lens. Moreover, the alteration of
MAP kinase activity in the lens is sufficient to cause cataract
formation with enlarged extracellular space and vacuoles in the
differentiating fibers. This transgenic mouse may provide a useful
model for understanding the mechanism(s) for some aspects of human
This PDF is available to Subscribers Only