Retinal degeneration in mice lacking the gamma subunit of the rod cGMP phosphodiesterase

Science. 1996 May 17;272(5264):1026-9. doi: 10.1126/science.272.5264.1026.


The retinal cyclic guanosine 3',5'-monophosphate (cGMP) phosphodiesterase (PDE) is a key regulator of phototransduction in the vertebrate visual system. PDE consists of a catalytic core of alpha and beta subunits associated with two inhibitory gamma subunits. A gene-targeting approach was used to disrupt the mouse PDEgamma gene. This mutation resulted in a rapid retinal degeneration resembling human retinitis pigmentosa. In homozygous mutant mice, reduced rather than increased PDE activity was apparent; the PDEalphabeta dimer was formed but lacked hydrolytic activity. Thus, the inhibitory gamma subunit appears to be necessary for integrity of the photoreceptors and expression of PDE activity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / deficiency
  • 3',5'-Cyclic-GMP Phosphodiesterases / genetics
  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism*
  • Animals
  • Base Sequence
  • Chimera
  • Crosses, Genetic
  • Cyclic GMP / metabolism*
  • Electroretinography
  • Enzyme Activation
  • Female
  • Gene Targeting
  • Humans
  • Light
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Retina / metabolism
  • Retina / pathology*
  • Retina / physiopathology
  • Retinal Degeneration / enzymology*
  • Retinal Degeneration / pathology
  • Retinal Degeneration / physiopathology
  • Retinal Rod Photoreceptor Cells / enzymology*
  • Retinal Rod Photoreceptor Cells / metabolism
  • Retinal Rod Photoreceptor Cells / pathology
  • Retinitis Pigmentosa / pathology


  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic GMP