Expression of a truncated FGF receptor results in defective lens development in transgenic mice.
Members of the fibroblast growth factor (FGF) family are thought to initiate biological responses through the activation of cell surface receptors which must dimerize to transmit an intracellular signal. Mammalian lens epithelial cells respond to exogenous extracellular FGF, either in tissue culture or in transgenic mice, by initiating fiber cell differentiation. The role of FGF signalling in normal lens development was evaluated by lens-specific synthesis of a kinase-deficient FGF receptor type I (FGFR1) in transgenic mice. This truncated FGF receptor is 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 reaction amplification of reverse transcribed lens RNA (RT-PCR). The presence of transgenic protein was determined by Western blotting with antibodies 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 microphthalmic lenses displayed a normal pattern of differentiation-specific crystallin expression, the lens epithelial cells were reduced in number and 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.
Robinson
M L
ML
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
MacMillan-Crow
L A
LA
Thompson
J A
JA
Overbeek
P A
PA
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000196:embryology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors