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.
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.
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.
CNGB1 mutant dogs have a residual ERG response from desensitized rods. This may be due to low levels of CNGA1 in outer segments.
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.
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.
CNGB1 mutant dogs have a residual ERG response from desensitized rods. This may be due to low levels of CNGA1 in outer segments.
摘要：
环核苷酸门控（CNG）通道β亚基（CNGB1）的突变是隐性视网膜色素变性的重要原因。我们鉴定了具有CNGB1截短突变的大型动物模型。这项研究报告了小的持久性，该模型中脱敏的杆ERG反应。
黑暗-,在CNGB1突变犬以及年龄和品种匹配的对照中记录光适应和彩色ERG。与已知完全缺乏杆功能的狗模型进行了比较；杆状磷酸二酯酶6α亚基（PDE6A-/-）突变的幼犬。进行免疫组织化学(IHC)以标记棒CNGα(CNGA1)和CNGB1亚基。
CNGB1突变犬的暗适应ERG具有升高的应答阈值,其中缺乏正常杆应答和剩余的视锥应答。刺激强度的增加导致了单独的外观，更慢的正波形跟随暗适应锥b波。随着刺激强度的增加，振幅增加，并与初始b波合并的速度更快。PDE6A-/-（仅视锥犬）与CNGB1突变犬对红色和蓝色闪光的反应以及暗适应和光适应反应之间的反应比较支持以下假设：CNGB1突变犬具有残留的脱敏杆状反应。CNGB1突变犬在外片段中具有可检测到的少量CNGA1。
CNGB1突变犬具有来自脱敏棒的残余ERG应答。这可能是由于在外段中的低水平的CNGA1。
黑暗-,在CNGB1突变犬以及年龄和品种匹配的对照中记录光适应和彩色ERG。与已知完全缺乏杆功能的狗模型进行了比较；杆状磷酸二酯酶6α亚基（PDE6A-/-）突变的幼犬。进行免疫组织化学(IHC)以标记棒CNGα(CNGA1)和CNGB1亚基。
CNGB1突变犬的暗适应ERG具有升高的应答阈值,其中缺乏正常杆应答和剩余的视锥应答。刺激强度的增加导致了单独的外观，更慢的正波形跟随暗适应锥b波。随着刺激强度的增加，振幅增加，并与初始b波合并的速度更快。PDE6A-/-（仅视锥犬）与CNGB1突变犬对红色和蓝色闪光的反应以及暗适应和光适应反应之间的反应比较支持以下假设：CNGB1突变犬具有残留的脱敏杆状反应。CNGB1突变犬在外片段中具有可检测到的少量CNGA1。
CNGB1突变犬具有来自脱敏棒的残余ERG应答。这可能是由于在外段中的低水平的CNGA1。
