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Disregulation of ocular morphogenesis by lens-specific expression of FGF-3/int-2 in transgenic mice

Robinson, M.L., Ohtaka-Maruyama, C., Chan, C.-C., Jamieson, S., Dickson, C., Overbeek, P.A., and Chepelinsky, A.B. (1998) Disregulation of ocular morphogenesis by lens-specific expression of FGF-3/int-2 in transgenic mice. Developmental Biology, 198 (1). pp. 13-31. ISSN 0012-1606

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Abstract

FGF-3, originally named int-2, was discovered as an oncogene frequently activated in mammary carcinomas resulting from the chromosomal integration of the mouse mammary tumor virus (MMTV). Int-2 was later designated FGF-3 based on sequence homology with other members of the fibroblast growth factor (FGF) family. FGF-1 is the prototypical member of the FGF family, and is the only family member which activates all known FGF receptor isoforms. Transgenic mice expressing in the lens a form of FGF-1 engineered to be secreted show premature differentiation of the entire lens epithelium. In contrast, transgenic mice engineered to secrete FGF-2 in the lens do not undergo premature differentiation of the lens epithelium (C. M. Stolenet al.,1997,Development124, 4009–4017). To further assess the roles of FGFs and FGF receptors in lens development, the αA-crystallin promoter was used to target expression of FGF-3 to the developing lens of transgenic mice. The expression of FGF-3 in the lens rapidly induced epithelial cells throughout the lens to elongate and to express fiber cell-specific proteins including MIP and β-crystallins. This premature differentiation of the lens epithelium was followed by the degeneration of the entire lens. Since FGF-1 and FGF-3 can both activate one FGF receptor isoform (FGFR2 IIIb) that is not activated by FGF-2, these results suggest that activation of FGFR2 IIIb is sufficient to induce fiber cell differentiation throughout the lens epitheliumin vivo.Furthermore, transgenic lens cells expressing FGF-3 were able to induce the differentiation of neighboring nontransgenic lens epithelial cells in chimeric mice. Expression of FGF-3 in the lens also resulted in developmental alterations of the eyelids, cornea, and retina, and in the most severely affected transgenic lines, the postnatal appearance of intraocular glandular structu

Item Type:Article
Status:Published
Refereed:Yes
Glasgow Author(s):Jamieson, Dr Susan
Authors: Robinson, M.L., Ohtaka-Maruyama, C., Chan, C.-C., Jamieson, S., Dickson, C., Overbeek, P.A., and Chepelinsky, A.B.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine > Clinical Specialities
Journal Name:Developmental Biology
ISSN:0012-1606
ISSN (Online):1095-564X
Published Online:3 May 2002

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