Age-related changes in Cngb1-X1 knockout mice: Prolonged cone survival

Academic Article


  • The rod photoreceptor cGMP-gated cation channel has an essential role in phototransduction functioning as the primary point for calcium and sodium entry into the rod outer segment. The channel consists of two subunits, α and β. The α-subunit can function in isolation as an ion channel, and the β-subunit modulates channel activity and has a structural role. We previously reported that a mouse knockout (KO) of the β-subunit and related glutamic acid rich proteins (GARPs) attenuates rod function and causes structural alterations and slowly progressive retinal degeneration. Here, we have extended our functional analyses of the KO mice evaluating rod and cone function using the electroretinogram in mice up to 4 months of age. Retinal stratification is preserved in the knockout mice at 3 months, and a significant number of cones remain up to 7 months based on PNA staining of cone sheaths. Electroretinography of KO mice at 1 month old revealed a diminished darkadapted b-wave and normal light-adapted b-wave compared to wild-type mice. Over the next 3 months, both dark- and light-adapted b-wave amplitudes declined, but the reduction was greater for darkadapted b-wave amplitudes. In one-month-old mice, the critical flicker frequency (CFF) was substantially lower for the KO mice at scotopic intensities, but normal at photopic intensities. CFF values remained stable in the KO mice as the b-wave amplitudes decreased with age. Declining b-wave amplitudes confirm an RP phenotype of rod followed by cone degeneration. Flicker responses show that the cone circuits function normally at threshold despite significant losses in the maximum light-adapted b-wave amplitude. These results confirm that rods are marginally functional in the absence of the b-subunit and in addition show that CFF may be a more sensitive measure of remaining functional cone vision in animal models of RP undergoing progressive rod cone degeneration. © Springer-Verlag 2012.
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    Author List

  • Zhang Y; Rubin GR; Fineberg N; Huisingh C; McGwin G; Pittler SJ; Kraft TW
  • Start Page

  • 163
  • End Page

  • 175
  • Volume

  • 124
  • Issue

  • 3