myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses.
myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses.
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DOI：
10.1016/j.exer.2014.03.007
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发表时间：
2014-05
影响因子：
3.4
通讯作者：
Perkins, Brian D.
中科院分区：
文献类型：
--
作者：
Wasfy, Meagan M.;Matsui, Jonathan I.;Miller, Jessica;Dowling, John E.;Perkins, Brian D.
肌球蛋白VIIA(MYO7A)的突变导致Usher综合征1B(USH1B)，这种疾病的特征是感觉神经性听力损失和视力障碍的组合，称为视网膜色素变性(RP)。尽管存在USH1B的Shaker-1小鼠模型，但在其寿命期间只观察到视网膜的轻微缺陷。之前对斑马鱼水手突变体的研究发现，突变体中存在平衡和听力障碍，但视网膜表型尚未描述。斑马鱼水手突变体也携带myo7aa突变。我们发现Myo7aa−/−突变体的外核层(ONL)细胞死亡增加。虽然myo7aa−/−突变体在视动反射测试中保留了视觉行为，但视网膜电信号记录显示突变动物的a波和b波幅度都显著降低，但视网膜电信号阈值敏感度没有变化。免疫组织化学显示视杆细胞和蓝锥体视蛋白在Myo7aa−/−神经元中定位错误，视杆细胞特异性标记的表达减少，进一步证明了所观察到的光感受器变性代表了RP的早期阶段。此外，持续的光照会导致广泛的光感受器退化，并在视网膜色素上皮(RPE)上出现大洞。在视网膜感受器的视网膜运动或黑素小体在视网膜色素上皮内的迁移中没有观察到差异，这表明肌肉7aa−/−在硬骨鱼的这些过程中不起作用。这些结果表明斑马鱼myo7aa−/−突变体是一种有用的动物模型，可用于研究患有USH1B的人类的RP。
Mutations in myosin VIIa (MYO7A) cause Usher syndrome 1B (USH1B), a disease characterized by the combination of sensorineural hearing loss and visual impairment termed retinitis pigmentosa (RP). Although the shaker-1 mouse model of USH1B exists, only minor defects in the retina have been observed during its lifespan. Previous studies of the zebrafish mariner mutant, which also carries a mutation in myo7aa, revealed balance and hearing defects in the mutants but the retinal phenotype has not been described. We found elevated cell death in the outer nuclear layer (ONL) of myo7aa−/− mutants. While myo7aa−/− mutants retained visual behaviors in the optokinetic reflex (OKR) assay, electroretinogram (ERG) recordings revealed a significant decrease in both a- and b-wave amplitudes in mutant animals, but not a change in ERG threshold sensitivity. Immunohistochemistry showed mislocalization of rod and blue cone opsins and reduced expression of rod-specific markers in the myo7aa−/− ONL, providing further evidence that the photoreceptor degeneration observed represents the initial stages of the RP. Further, constant light exposure resulted in widespread photoreceptor degeneration and the appearance of large holes in the retinal pigment epithelium (RPE). No differences were observed in the retinomotor movements of the photoreceptors or in melanosome migration within the RPE, suggesting that myo7aa−/− does not function in these processes in teleosts. These results indicate that the zebrafish myo7aa−/− mutant is a useful animal model for the RP seen in humans with USH1B.
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DOI：
10.1073/pnas.1130432100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Gibbs, D;Kitamoto, J;Williams, DS
通讯作者：
Williams, DS
影响因子：
3.7
作者：
Colella P;Sommella A;Marrocco E;Di Vicino U;Polishchuk E;Garcia Garrido M;Seeliger MW;Polishchuk R;Auricchio A
通讯作者：
Auricchio A
DOI：
10.1111/j.1600-0854.2010.01085.x
发表时间：
2010-09
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Ile KE;Kassen S;Cao C;Vihtehlic T;Shah SD;Mousley CJ;Alb JG Jr;Huijbregts RP;Stearns GW;Brockerhoff SE;Hyde DR;Bankaitis VA
通讯作者：
Bankaitis VA
影响因子：
4.8
作者：
Jowett, T
通讯作者：
Jowett, T
DOI：
10.1073/pnas.92.23.10545
发表时间：
1995-11-07
影响因子：
11.1
作者：
BROCKERHOFF, SE;HURLEY, JB;DOWLING, JE
通讯作者：
DOWLING, JE