Retinal ablation and altered lens differentiation induced by ocular overexpression of BMP7.
The alphaA-crystallin promoter was used to target expression of bone morphogenetic protein 7 (BMP7) to lens fiber cells in transgenic mice. Surprisingly, lens-specific expression of BMP7 induced widespread apoptosis and rapid ablation of the neural retina in multiple families. Subsequent to retinal ablation, the lens bow region shifted posteriorly until lens epithelial cells completely enveloped the lens. Lens-specific expression of FGF3 was found to rescue the loss of fiber cell differentiation. Our results show that elevated BMP7 levels can induce rapid retinal degeneration accompanied by disruption of the endogenous ocular system for fiber cell induction.
Hung
Fang Cheng
FC
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Zhao
Shulei
S
Chen
Qin
Q
Overbeek
Paul A
PA
D000818:Animals; D017209:Apoptosis; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001947:Breeding; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007908:Lens, Crystalline / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012160:Retina / Q000196:embryology*; D012162:Retinal Degeneration / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors