title: c-abl is required for the development of hyperoxia-induced retinopathy.
abstract: The requirement for the nonreceptor tyrosine kinase c-abl in the pathogenesis of retinopathy of prematurity (ROP) was examined using the mouse model for ROP and c-abl-deficient mice. Hyperoxia-induced retinal neovascularization was observed in wild-type and heterozygous mice but animals that were homozygous null for c-abl did not develop a vasoproliferative retinopathy in response to hyperoxia. Two gene products, endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF), have been implicated in the pathogenesis of ROP. The mRNA expression of ET-1 and VEGF was assessed in mice maintained in normoxia and in hyperoxia-exposed mice. ET-1 mRNA levels were unchanged in wild-type mice throughout the hyperoxia treatment, suggesting that ET-1 mRNA expression is not regulated by the increase in inspired oxygen. In wild-type mice maintained in room air, VEGF mRNA levels rose threefold from postnatal day 6 (P6) to P17. When wild-type mice were treated with the hyperoxia regimen, a fivefold decrease in VEGF mRNA expression was observed from P7 to P16. However, retinal VEGF expression in hyperoxia-treated homozygous null mice did not decrease and remained at control levels. These data suggest that c-abl is required for the hyperoxia-induced retinal neovascularization and hyperoxia-induced decrease in VEGF mRNA levels.
authors: Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors: I
authors: I
authors: Nunes
authors: R D
authors: RD
authors: Higgins
authors: L
authors: L
authors: Zanetta
authors: P
authors: P
authors: Shamamian
authors: S P
authors: SP
authors: Goff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018496:Hyperoxia / Q000150:complications*; D007231:Infant, Newborn; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D019332:Endothelin-1; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016315:Proto-Oncogene Proteins c-abl