Kudo Takayuki, Wangemann Philine, Marcus Daniel C
Anatomy and Physiology Department, Kansas State University, 228 Coles Hall, Manhattan, KS, 66506, USA.
BMC Physiol. 2018 Jan 25;18(1):1. doi: 10.1186/s12899-018-0035-1.
Claudins are major components of tight junctions, which form the paracellular barrier between the cochlear luminal and abluminal fluid compartments that supports the large transepithelial voltage difference and the large concentration differences of K, Na and Ca needed for normal cochlear function. Claudins are a family of more than 20 subtypes, but our knowledge about expression and localization of each subtype in the cochlea is limited.
We examined by quantitative RT-PCR the expression of the mRNA of 24 claudin isoforms in mouse cochlea during postnatal development and localized the expression in separated fractions of the cochlea. Transcripts of 21 claudin isoforms were detected at all ages, while 3 isoforms (Cldn-16, - 17 and - 18) were not detected. Claudins that increased expression during development include Cldn-9, - 13, - 14, - 15, and -19v2, while Cldn-6 decreased. Those that do not change expression level during postnatal development include Cldn-1, - 2, - 3, - 4, - 5, - 7, - 8, -10v1, -10v2, - 11, - 12, -19v1, - 20, - 22, and - 23. Our investigation revealed unique localization of some claudins. In particular, Cldn-13 expression rapidly increases during early development and is mainly expressed in bone but only minimally in the lateral wall (including stria vascularis) and in the medial region (including the organ of Corti). No statistically significant changes in expression of Cldn-11, - 13, or - 14 were found in the cochlea of Slc26a4 mice compared to Slc26a4 mice.
We demonstrated developmental patterns of claudin isoform transcript expression in the murine cochlea. Most of the claudins were associated with stria vascularis and organ of Corti, tissue fractions rich in tight junctions. However, this study suggests a novel function of Cldn-13 in the cochlea, which may be linked to cochlear bone marrow maturation.
紧密连接蛋白是紧密连接的主要组成部分，紧密连接在耳蜗管腔和管腔外液腔之间形成细胞旁屏障，维持着正常耳蜗功能所需的大的跨上皮电压差以及钾、钠和钙的大浓度差。紧密连接蛋白是一个包含20多种亚型的家族，但我们对每种亚型在耳蜗中的表达和定位了解有限。
我们通过定量逆转录聚合酶链反应检测了出生后发育过程中小鼠耳蜗中24种紧密连接蛋白亚型的mRNA表达，并将其定位到耳蜗的不同部分。在所有年龄段均检测到21种紧密连接蛋白亚型的转录本，而未检测到3种亚型（Cldn-16、-17和-18）。发育过程中表达增加的紧密连接蛋白包括Cldn-9、-13、-14、-15和-19v2，而Cldn-6表达减少。出生后发育过程中表达水平不变的包括Cldn-1、-2、-3、-4、-5、-7、-8、-10v1、-10v2、-11、-12、-19v1、-20、-22和-23。我们的研究揭示了一些紧密连接蛋白的独特定位。特别是，Cldn-13在早期发育过程中表达迅速增加，主要表达于骨中，而在外侧壁（包括血管纹）和内侧区域（包括柯蒂氏器）中表达极少。与野生型小鼠相比，在Slc26a4基因敲除小鼠的耳蜗中，Cldn-11、-13或-14的表达没有统计学上的显著变化。
我们证明了小鼠耳蜗中紧密连接蛋白亚型转录本的发育模式。大多数紧密连接蛋白与血管纹和柯蒂氏器相关，这些组织部分富含紧密连接。然而，本研究提示Cldn-13在耳蜗中具有新功能，这可能与耳蜗骨髓成熟有关。
