The Porcine Chloride Channel Calcium-Activated Family Member pCLCA4a Mirrors Lung Expression of the Human hCLCA4
The Porcine Chloride Channel Calcium-Activated Family Member pCLCA4a Mirrors Lung Expression of the Human hCLCA4
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DOI：
10.1369/0022155411426455
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发表时间：
2012-01-01
影响因子：
3.2
通讯作者：
Mundhenk, Lars
中科院分区：
文献类型：
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作者：
Plog, Stephanie;Groetzsch, Tanja;Mundhenk, Lars
最近已经建立了囊性纤维化（CF）的猪模型，其预期比小鼠模型更接近于模拟人类疾病。人类CLCA（最初命名为氯离子通道，钙激活）成员hCLCA 4被认为是CF疾病严重程度的潜在修饰剂，但其鼠直系同源物mCLCA 6在小鼠肺中不表达。在这里，我们的特点是基因组结构，蛋白质加工，和组织表达模式的猪直系同源hCLCA 4，pCLCA 4a。发现pCLCA 4a的基因组结构和细胞蛋白质加工与hCLCA 4和mCLCA 6的基因组结构和细胞蛋白质加工密切相关。与人肺组织相似，pCLCA 4a mRNA在猪肺组织中有强表达，pCLCA 4a蛋白在气管和支气管上皮细胞的顶膜上有表达。这与小鼠mCLCA 6形成鲜明对比，小鼠mCLCA 6仅在肠上皮细胞中检测到，而在鼠肺中未检测到。这些结果可能有助于理解CF表型中的物种特异性差异，并支持CF猪模型可能比小鼠模型更适合研究hCLCA 4的作用的观点。（J Histochem Cytochem 60：45-56，2012）
Pig models of cystic fibrosis (CF) have recently been established that are expected to mimic the human disease closer than mouse models do. The human CLCA (originally named chloride channels, calcium-activated) member hCLCA4 is considered a potential modifier of disease severity in CF, but its murine ortholog, mCLCA6, is not expressed in the mouse lung. Here, we have characterized the genomic structure, protein processing, and tissue expression patterns of the porcine ortholog to hCLCA4, pCLCA4a. The genomic structure and cellular protein processing of pCLCA4a were found to closely mirror those of hCLCA4 and mCLCA6. Similar to human lung, pCLCA4a mRNA was strongly expressed in porcine lungs, and the pCLCA4a protein was immunohistochemically detected on the apical membranes of tracheal and bronchial epithelial cells. This stands in sharp contrast to mouse mCLCA6, which has been detected exclusively in intestinal epithelia but not the murine lung. The results may add to the understanding of species-specific differences in the CF phenotype and support the notion that the CF pig model may be more suitable than murine models to study the role of hCLCA4. (J Histochem Cytochem 60:45-56, 2012)