In vivo studies of the γ subunit of retinal cGMP-phophodiesterase with a substitution of tyrosine-84

S. H. Tsang, C. K. Yamashita, K. Doi, D. J. Salchow, N. Bouvier, M. Mendelsohn, P. Gouras, D. B. Farber, S. P. Goff

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The inhibitory rod cGMP phosphodiesterase γ subunit (PDEγ) is a major component of the photoresponse and is required to support rod integrity. Pdegtm1/Pdegtm1 mice (which lack PDEγ owing to a targeted disruption of the Pdeg gene) suffer from a very rapid and severe photoreceptor degeneration. The Y84G (Tyr84→Gly) allele of PDEγ has previously been shown in experiments carried out in vitro to reduce the regulatory control of the PDE catalytic core (PDEαβ) exerted by the wild-type γ subunit. To determine the effects of this mutation on in viva function, the murine opsin promoter was used to direct expression to the photoreceptors of +/Pdegtm1 mice of a mutant Y84G and a wild-type PDEγ control transgene. The transgenic mice were crossed with Pdegtm1/Pdegtm1 mice to generate animals able to synthesize only the transgenic PDEγ. Our results showed that wild-type PDEγ and Y84G transgenes could complement the Pdegtm1/Pdegtm1 mutant for photoreceptor survival. The mutation caused a significant biochemical defect in PDE activation by transducin. However, the Y84G mutation did not fully eliminate the control of PDEγ on the PDE catalytic core in viva; the expression of the mutant subunit was associated with only a 10-fold reduction in the amplitude of the a-wave and a 1.5-fold decrease in the b-wave of the corneal electroretinogram. Unexpectedly, the mutation caused a much 'milder' phenotype in vivo than was predicted from the biochemical assays in vitro.

Original languageEnglish
Pages (from-to)467-474
Number of pages8
JournalBiochemical Journal
Issue number3
StatePublished - 1 Feb 2001
Externally publishedYes


  • Knockout animals
  • Phosphodiesterase
  • Photoreceptor transduction
  • Retinal degeneration
  • Transgenic animals


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