title: Cell type-specific effects of Rb deletion in the murine retina.
abstract: Certain cells of the human retina are extremely sensitive to loss of function of the retinoblastoma tumor suppressor gene RB. Retinoblastomas develop early in life and at high frequency in individuals heterozygous for a germ-line RB mutation, and sporadic retinoblastomas invariably have somatic mutation in the RB gene. In contrast, retinoblastomas do not develop in Rb+/- mice. Although retinoblastoma is thought to have developmental origins, the function of Rb in retinal development has not been fully characterized. Here we studied the role of Rb in normal retinal development and in retinoblastoma using conditional Rb mutations in the mouse. In late embryogenesis, Rb-deficient retinas exhibited ectopic S-phase and high levels of p53-independent apoptosis, particularly in the differentiating retinal ganglion cell layer. During postnatal retinal development, loss of Rb led to more widespread retinal apoptosis, and adults showed loss of photoreceptors and bipolar cells. Conditional Rb mutation in the retina did not result in retinoblastoma formation even in a p53-mutant background. However, on a p107- or p130-deficient background, Rb mutation in the retina caused retinal dysplasia or retinoblastoma.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: David
authors.initials: D
authors.lastname: MacPherson
authors.forename: Julien
authors.initials: J
authors.lastname: Sage
authors.forename: Teresa
authors.initials: T
authors.lastname: Kim
authors.forename: Dennis
authors.initials: D
authors.lastname: Ho
authors.forename: Margaret E
authors.initials: ME
authors.lastname: McLaughlin
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D003433:Crosses, Genetic; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D016161:Genes, Retinoblastoma / Q000235:genetics*; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012160:Retina / Q000196:embryology* / Q000254:growth & development* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130
chemical_list: D009687:Nuclear Proteins; D011506:Proteins; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D019938:Cyclin D1