Department of Ophthalmology, Semmelweis University, Budapest, Hungary; Department of Experimental Psychology, University of Sao Paulo, Sao Paulo, Brazil.
Department of Experimental Psychology, University of Sao Paulo, Sao Paulo, Brazil.
Neurobiol Dis. 2021 May;152:105288. doi: 10.1016/j.nbd.2021.105288. Epub 2021 Feb 5.
The mdx52 mouse model of Duchenne muscular dystrophy (DMD) is lacking exon 52 of the DMD gene that is located in a hotspot mutation region causing cognitive deficits and retinal anomalies in DMD patients. This deletion leads to the loss of the dystrophin proteins, Dp427, Dp260 and Dp140, while Dp71 is preserved. The flash electroretinogram (ERG) in mdx52 mice was previously characterized by delayed dark-adapted b-waves. A detailed description of functional ERG changes and visual performances in mdx52 mice is, however, lacking. Here an extensive full-field ERG repertoire was applied in mdx52 mice and WT littermates to analyze retinal physiology in scotopic, mesopic and photopic conditions in response to flash, sawtooth and/or sinusoidal stimuli. Behavioral contrast sensitivity was assessed using quantitative optomotor response (OMR) to sinusoidally modulated luminance gratings at 100% or 50% contrast. The mdx52 mice exhibited reduced amplitudes and delayed implicit times in dark-adapted ERG flash responses, particularly in their b-wave and oscillatory potentials, and diminished amplitudes of light-adapted flash ERGs. ERG responses to sawtooth stimuli were also diminished and delayed for both mesopic and photopic conditions in mdx52 mice and the first harmonic amplitudes to photopic sine-wave stimuli were smaller at all temporal frequencies. OMR indices were comparable between genotypes at 100% contrast but significantly reduced in mdx52 mice at 50% contrast. The complex ERG alterations and disturbed contrast vision in mdx52 mice include features observed in DMD patients and suggest altered photoreceptor-to-bipolar cell transmission possibly affecting contrast sensitivity. The mdx52 mouse is a relevant model to appraise the roles of retinal dystrophins and for preclinical studies related to DMD.
mdx52 肌营养不良（DMD）小鼠模型缺失 DMD 基因的外显子 52，该基因位于热点突变区域，导致 DMD 患者认知缺陷和视网膜异常。这种缺失导致抗肌萎缩蛋白（dystrophin）蛋白 DP427、DP260 和 DP140 的丢失，而 DP71 得以保留。此前，mdx52 小鼠的闪光视网膜电图（ERG）表现为暗适应 b 波延迟。然而，关于 mdx52 小鼠 ERG 功能变化和视力表现的详细描述尚缺乏。在这里，我们在 mdx52 小鼠和 WT 同窝仔鼠中应用了广泛的全视野 ERG 谱，以分析暗适应、中间适应和明适应条件下闪光、锯齿波和/或正弦波刺激的视网膜生理学。通过使用正弦调制亮度光栅的定量光动反应（OMR）评估行为对比敏感度，光栅对比度为 100%或 50%。mdx52 小鼠在暗适应 ERG 闪光反应中表现出振幅降低和潜伏期延迟，尤其是 b 波和眼动电位，以及明适应闪光 ERG 的振幅降低。锯齿波刺激的 ERG 反应在 mdx52 小鼠的中间适应和明适应条件下也降低且延迟，在所有时间频率下，明适应正弦波刺激的第一谐波振幅都较小。两种基因型在 100%对比度时 OMR 指数相当，但在 50%对比度时 mdx52 小鼠显著降低。mdx52 小鼠的复杂 ERG 改变和视力障碍包括 DMD 患者中观察到的特征，表明光感受器-双极细胞传递改变，可能影响对比敏感度。mdx52 小鼠是评估视网膜肌营养不良蛋白作用和与 DMD 相关的临床前研究的相关模型。
