Disruption of a retinal guanylyl cyclase gene leads to cone-specific dystrophy and paradoxical rod behavior

J Neurosci. 1999 Jul 15;19(14):5889-97. doi: 10.1523/JNEUROSCI.19-14-05889.1999.


One of two orphan photoreceptor guanylyl cyclases that are highly conserved from fish to mammals, GC-E (or retGC1) was eliminated by gene disruption. Expression of the second retinal cyclase (GC-F) as well as the numbers and morphology of rods remained unchanged in GC-E null mice. However, rods isolated from such mice, despite having a normal dark current, recovered from a light flash markedly faster. Unexpectedly, the a- and b-waves of electroretinograms (ERG) from dark-adapted null mice were suppressed markedly. Cones, initially present in normal numbers in the retina, disappeared by 5 weeks, based on ERG and histology. Thus, the GC-E-deficient mouse defines a model for cone dystrophy, but it also demonstrates that morphologically normal rods display paradoxical behavior in their responses to light.

Publication types

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

MeSH terms

  • Adaptation, Ocular
  • Animals
  • Darkness
  • Electroretinography
  • Exons
  • Guanylate Cyclase / deficiency
  • Guanylate Cyclase / genetics*
  • Guanylate Cyclase / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Restriction Mapping
  • Retina / enzymology*
  • Retinal Cone Photoreceptor Cells / pathology
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Rod Photoreceptor Cells / pathology
  • Retinal Rod Photoreceptor Cells / physiology*
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology
  • Retinitis Pigmentosa / physiopathology


  • Guanylate Cyclase