Residual rod function in CNGB1 mutant dogs.
Residual rod function in CNGB1 mutant dogs.
复制标题
CNGB1 突变狗的残余杆功能。
DOI：
10.1007/s10633-022-09899-3
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Winkler,PaigeA
中科院分区：
文献类型：
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作者：
Petersen-Jones,SimonM;Pasmanter,Nathaniel;Occelli,LaurenceM;Querubin,JaniceR;Winkler,PaigeA
目的环核苷酸门控（CNG）通道β亚基（CNGB 1）突变是隐性视网膜色素变性的重要原因。我们确定了一个大型动物模型与截断突变CNGB 1。本研究报告的持久性小，脱敏杆ERG responses in this model.MethodsDark，光适应和彩色ERG记录在CNGB 1突变狗和年龄和品种匹配的控制。与已知完全缺乏视杆功能的犬模型进行比较;在视杆磷酸二酯酶6 α亚基（PDE 6A −/−）中具有突变的年轻犬。免疫组织化学（IHC）标记杆CNG α（CNGA 1）和CNGB 1亚基performed.ResultsThe CNGB 1突变狗的暗适应ERG的反应阈值提高，缺乏正常的杆反应和剩余的锥反应。增加刺激强度导致出现一个单独的，较慢的正波形后，黑暗适应锥b波。随着刺激强度的增加，其振幅增加，并且与初始b波合并的速度更快。通过比较PDE 6A −/−（仅视锥细胞）和CNGB 1突变体狗对红光和蓝光的反应以及暗适应和光适应反应，支持CNGB 1突变体狗存在残余的视杆细胞脱敏反应的假设;在CNGB 1突变体狗的外节中检测到少量的CNGA 1。这可能是由于外节中CNGA 1水平较低。
PurposeMutations 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 ofCNGB1. This study reports the persistence of small, desensitized rod ERG responses in this model.MethodsDark-, light-adapted and chromatic ERGs were recorded inCNGB1mutant 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.ResultsThe dark-adapted ERG ofCNGB1mutant 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 fromPDE6A−/−(cone only dogs) withCNGB1mutant dogs to red and blue flashes and between dark-adapted and light-adapted responses supported the hypothesis that theCNGB1mutant dog had residual desensitized rod responses.CNGB1mutant dogs had a small amount of CNGA1 detectable in the outer segments.ConclusionsCNGB1mutant dogs have a residual ERG response from desensitized rods. This may be due to low levels of CNGA1 in outer segments.