Abstract
BackgroundClaudins 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 Ca2+ 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.ResultsWe 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.ConclusionsWe 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.
Highlights
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 Ca2+ needed for normal cochlear function
Transcripts of 21 claudin isoforms were detected at all ages, while 3 isoforms (Cldn-16, − 17 and − 18) were not detected (Fig. 2)
We examined RNA from whole cochleae from age- and sex-matched littermates of Slc26a4+/− and Slc26a4−/− and analyzed by two-way analysis of variance (ANOVA) 1) Cldn11, which is expressed in basal cells of stria vascularis [12], and whose deletion in mice causes hearing loss, 2) Cldn-13, which is expressed in cochlear outer bone, and 3) Cldn-14, which is expressed in organ of Corti and is responsible for human hereditary deafness DFNB29
Summary
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 Ca2+ needed for normal cochlear function. Tight junctions are structures consisting of proteins that join epithelial and endothelial cells to form continuous sheets and tubules which separate two liquid compartments. They consist of claudins [1], occludins [2] and other proteins that form a band-like network known as tight junction strands. These junctions are known to perform several functions (barrier, pore and fence), and are composed of several types of proteins: transmembrane (e.g., claudins and occludin), cytoplasmic, signaling and adapter links to the cytoskeleton [1, 3]. The fence function refers to the restriction of lateral movement of membrane proteins and lipids within the face of the plasma membrane, which retains the separate physiological functions of the luminal and abluminal cell membranes that are necessary to carry out vectorial transport of solutes and water
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