{Reference Type}: Journal Article
{Title}: Residual rod function in CNGB1 mutant dogs.
{Author}: Petersen-Jones SM;Pasmanter N;Occelli LM;Querubin JR;Winkler PA;
{Journal}: Doc Ophthalmol
{Volume}: 145
{Issue}: 3
{Year}: 12 2022
{Factor}: 1.854
{DOI}: 10.1007/s10633-022-09899-3
{Abstract}: Mutations in the cyclic nucleotide-gated (CNG) channel beta subunit (CNGB1) are an important cause of recessive retinitis pigmentosa. We identified a large animal model with a truncating mutation of CNGB1. This study reports the persistence of small, desensitized rod ERG responses in this model.<BR>Dark-, light-adapted and chromatic ERGs were recorded in CNGB1 mutant dogs and age and breed matched controls. Comparisons were made with a dog model known to completely lack rod function; young dogs with a mutation in the rod phosphodiesterase 6 alpha subunit (PDE6A-/-). Immunohistochemistry (IHC) to label the rod CNG alpha (CNGA1) and CNGB1 subunits was performed.<BR>The dark-adapted ERG of CNGB1 mutant dogs had a raised response threshold with lack of normal rod response and a remaining cone response. Increasing stimulus strength resulted in the appearance of a separate, slower positive waveform following the dark-adapted cone b-wave. With increasing stimulus strength this increased in amplitude and became faster to merge with the initial b-wave. Comparison of responses from PDE6A-/- (cone only dogs) with CNGB1 mutant dogs to red and blue flashes and between dark-adapted and light-adapted responses supported the hypothesis that the CNGB1 mutant dog had residual desensitized rod responses. CNGB1 mutant dogs had a small amount of CNGA1 detectable in the outer segments.<BR>CNGB1 mutant dogs have a residual ERG response from desensitized rods. This may be due to low levels of CNGA1 in outer segments.