Department of Biology, Developmental, Cell and Molecular Biology Group, Duke University, French Science Research Center, Durham, North Carolina, USA.
Ear Hear. 2010 Oct;31(5):714-21. doi: 10.1097/AUD.0b013e3181ddf5a3.
Human mutations in the DNA repair genes, Xeroderma pigmentosum (XP)-C and XPA result in hearing loss, which has fueled the hypothesis that there is a significant demand for these genes in protecting cochlear genetic material. Therefore, we quantified the level of XPC and XPA mRNA in the mammalian cochlea.
XPC and XPA mRNAs were purified from the cochlea of 15 Fischer344 rats and quantified using SYBR Green chemistry. Another 15 Fischer344 rats were sacrificed for immunolocalization of XPC and XPA polypeptides in the cochlea and kidney (control organ).
XP mRNA levels were up to 95% (XPA) and 69% (XPC) of the respective maximum expression capacity of each gene. In addition, these cochlear levels were up to sixfold (XPC) and threefold (XPA) greater than that of the kidney, which is known to exhibit XP-DNA repair activity that is greater than most organs of the body. Immunohistochemistry revealed that most kidney and cochlear cells were immunopositive.
These data suggest that under normal conditions the cochlea is experiencing persistent genomic stress that helps to explain the hypersensitivity of the cochlea to exogenous stressors (ototoxic xenobiotics and/or acoustic-overexposure) as well as provide a basis to interpret hearing loss among patients with XP.
人源 Xeroderma pigmentosum (XP)-C 和 XPA 等 DNA 修复基因的突变会导致听力损失，这一现象推动了这样一种假说，即这些基因在保护耳蜗遗传物质方面有很大的需求。因此，我们对哺乳动物耳蜗中的 XPC 和 XPA mRNA 水平进行了定量分析。
从 15 只 Fischer344 大鼠的耳蜗中纯化 XPC 和 XPA mRNA，并使用 SYBR Green 化学法进行定量。另外 15 只 Fischer344 大鼠被处死，用于耳蜗和肾脏（对照器官）中 XPC 和 XPA 多肽的免疫定位。
XP mRNA 的水平高达每个基因最大表达能力的 95%（XPA）和 69%（XPC）。此外，这些耳蜗水平比已知具有比身体大多数器官都高的 XP-DNA 修复活性的肾脏高 6 倍（XPC）和 3 倍（XPA）。免疫组织化学显示，大多数肾脏和耳蜗细胞呈免疫阳性。
这些数据表明，在正常情况下，耳蜗会持续受到基因组压力的影响，这有助于解释耳蜗对外源性应激源（耳毒性异生物质和/或声过度暴露）的敏感性增加，并为解释 XP 患者的听力损失提供了依据。
