Cell type-specific effects of Rb deletion in the murine retina (original) (raw)

  1. David MacPherson1,2,
  2. Julien Sage1,2,4,
  3. Teresa Kim1,2,
  4. Dennis Ho1,2,
  5. Margaret E. McLaughlin1,2, and
  6. Tyler Jacks1,3,5
  7. 1Department of Biology and 2Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; 3Howard Hughes Medical Institute, Chevy Chase, Maryland 20185, USA

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.

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