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T. W. Kraft, G. R. Rubin, Y. Zhang, S. J. Pittler; Age-Related ERG Changes in Cngb1-X1 Knockout Mice: Cone Survival. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4760.
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The rod cyclic nucleotide gated channel (CNGC1) comprised of and β subunits is critical to regulating ion flow during phototransduction. To examine retina function in the absence of the β subunit we analyzed a β subunit knockout (KO) mouse model (Cngb1-x1) using the full field corneal electroretinogram.
We measured the standard ERG intensity response function, a- and b-wave responses to bright white flashes under dark-adapted conditions and on a rod-saturating background, and photopic and scotopic flicker ERG CFFs.
KO mice exhibit diminished a- and b-wave amplitudes compared to WT mice. At 1-month old the dark-adapted a- and b-wave amplitudes in KO mice are 1/8 and 1/2 of WT mice. The light-adapted a-wave in 1-month old KO mice measures 1/6 the amplitude of WT mice, however the b-wave is relatively normal. Over the next 3 months dark- and light-adapted b-wave amplitudes continue to decline in contrast to wild type or heterozygotes. The decline was relatively greater for dark-adapted b-wave amplitudes, indicating a more rapid loss of rod function. From the intensity response series we found1-month KO mice to be 26 fold less sensitive than WT mice. This result is consistent with previous single cell recordings (Zhang et al, 2008). Recovery of the b-wave as a function of the interstimulus interval (ISI) between multiple flashes, demonstrated a greater b-wave recovery in KO mice for an ISI of 16 sec or less. The critical flicker frequency (CFF) was measured to assess rod and cone function at threshold. The CFF was lower for the KO mice at scotopic intensities and equal to wild type at photopic intensities. CFF values remained remarkably stable in the KO mice while b-wave amplitudes decreased.
Rod photoreceptors are functional at greatly reduced sensitivity in the β subunit KO mouse. The flicker ERG result suggests that the remaining cones are functionally normal at threshold, but the cone-driven b-wave maximum is reduced.
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