Ml. Robinson et al., EXPRESSION OF A TRUNCATED FGF RECEPTOR RESULTS IN DEFECTIVE LENS DEVELOPMENT IN TRANSGENIC MICE, Development, 121(12), 1995, pp. 3959-3967
Members of the fibroblast growth factor (FGF) family are thought to in
itiate biological responses through the activation of cell surface rec
eptors which must dimerize to transmit an intracellular signal. Mammal
ian lens epithelial cells respond to exogenous extracellular FGF, eith
er in tissue culture or in transgenic mice, by initiating fiber cell d
ifferentiation. The role of FGF signalling in normal lens development
was evaluated by lens-specific synthesis of a kinase-deficient FGF rec
eptor type I (FGFR1) in transgenic mice. This truncated FGF receptor i
s thought to act as a dominant negative protein by heterodimerization
with endogenous FGF receptors. The presence of transgenic mRNA in the
lens was confirmed by in situ hybridization and by polymerase chain re
action amplification of reverse transcribed lens RNA (RT-PCR). The pre
sence of transgenic protein was determined by Western blotting with an
tibodies to an extracellular domain of FGFR1. Three of four transgenic
families expressing the truncated FGF receptor exhibited lens defects
ranging from cataracts to severe microphthalmia. While the microphtha
lmic lenses displayed a normal pattern of differentiation-specific cry
stallin expression, the lens epithelial cells were reduced in number a
nd the lens fiber cells displayed characteristics consistent with the
induction of apoptosis. Our results support the view that FGF receptor
signalling plays an essential role in normal lens biology.