Age-related functional and histopathological changes of the ear in the MPS I mouse
Age-related functional and histopathological changes of the ear in the MPS I mouse
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DOI：
10.1016/j.ijporl.2006.09.016
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发表时间：
2007-02-01
影响因子：
1.5
通讯作者：
Whitley, Chester B.
中科院分区：
文献类型：
--
作者：
Schachern, Patricia A.;Cureoglu, Sebahattin;Whitley, Chester B.
目的：粘多糖样变性I型（MPS I）是一种常染色体隐性遗传疾病，由编码酶α-L-艾杜糖醛酸酶的基因突变引起。这种酶负责降解硫酸皮肤素和硫酸乙酰肝素。酶缺乏导致它们在几乎所有器官的溶酶体中积累，导致严重的躯体和神经变化。中耳炎合并混合性听力损失的临床表现很常见。耳病理和听力损失的细胞和分子机制尚不清楚。方法：采用1-32 kHz短纯音和短纯音诱发的听性脑干反应（ABR），对53只小鼠进行光镜和电镜观察，观察其中耳和内耳的病理变化。（1）野生型（+/+）-2个月时5个，4-6个月时5个，13-19个月时5个;（2）杂合子（+/-）-2个月时4个，4-6个月时5个，13-19个月时8个;（3）纯合子（-/-）-2月龄5例，4-6月龄6例，13-19月龄5例。组织学也做了5个新生-/- mice.Results：在新生儿，没有溶酶体储存观察和耳朵出现年龄适当的正常。在所有其他-/-小鼠中，在螺旋韧带、螺旋突起、螺旋利姆布斯、基底膜、Reissner膜的上皮细胞和间皮细胞、血管内皮细胞和一些神经节细胞中观察到具有溶酶体储存空泡的细胞;它们的数量随着年龄的增长而增加。在2或6个月时未观察到毛细胞损失，但在1岁小鼠中Corti器官完全丧失。与+/+和+/-小鼠相比，-/-小鼠的听力在所有年龄均显著降低。听力损失的进展从轻度到中度损失在2个月至深刻的6个月和总聋1岁age.Conclusions：渐进的年龄相关的变化，建议早期治疗干预，以防止感觉细胞损伤和听力损失。(C)2006爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by a mutation in the gene encoding the enzyme alpha-L-iduronidase. This enzyme is responsible for degradation of dermatan and heparan sulfates. Enzyme deficiency results in their accumulation in lysosomes of virtually all organs, resulting in severe somatic and neurological changes. Clinical findings of otitis media with mixed hearing loss are common. Cellular and molecular mechanisms of ear pathology and hearing loss are not understood. The purpose of this study is to describe the age-related audiologic and histopathologic changes of the ear in the mouse model of MPS I.Methods: Auditory brainstem responses (ABR) were obtained to clicks and tone bursts at 1-32 kHz, and pathological changes to middle and inner ears were studied with light and electron microscopy in 53 mice that included: (1) wild type (+/+)-five at 2 months, five at 4-6 months, and five at 13-19 months; (2) heterozygotes (+/-)-four at 2 months, five at 4-6 months, and eight at 13-19 months; and (3) homozygotes (-/-)-five at 2 months, six at 4-6 months, and five at 13-19 months. Histopathology was also done on five newborn -/- mice.Results: In newborns, no lysosomal storage was observed and the ear appeared age appropriately normal. In all other -/- mice, cells with lysosomal storage vacuoles were observed in spiral ligament, spiral prominence, spiral limbus, basilar membrane, epithelial and mesothelial cells of Reissner's membrane, endothelial cells of vessels, and some ganglion cells; their number increased with aging. Hair cell loss was not observed at 2 or 6 months, but there was total loss of the organ of Corti in year-old mice. Hearing of -/- mice was significantly decreased at all ages compared to +/+ and +/-. Hearing loss progressed from mild to moderate loss at 2 months to profound at 6 months and total deafness by 1 year of age.Conclusions: Progressive age-related changes suggest early therapeutic intervention to prevent sensory cell damage and hearing loss. (C) 2006 Elsevier Ireland Ltd. All rights reserved.