Quantitative expression analyses of candidates for alternative anion conductance in cystic fibrosis mouse models

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• 作者：Josephine Braun ; Lars Mundhenk ; Friederike Range ; Achim D. Gruber
• 关键词：Bestrophin ; CLC ; CLCA ; Cystic fibrosis ; mTTYH3 ; TMEM16
• 刊名：Journal of Cystic Fibrosis
• 出版年：2010
• 出版时间：September 2010
• 年：2010
• 卷：9
• 期：5
• 页码：351-364
• 全文大小：1648 K

文摘

Background

Diversity of cystic fibrosis (CF) phenotype in patients with the same CFTR-mutation raised the hypothesis that other factors modulate the phenotype including “alternativeȁd; calcium-activated anion currents (CaCC). This study compares the mRNA expression levels of candidate CaCC mediators in CF mouse models with wild type controls.

Methods

mBEST1, mBEST2, mCLC-3B, mCLC-4, mTTYH3, mTMEM16A, mTMEM16F, mTMEM16K, mCLCA1 to -6 and SLC26A9 mRNA were quantified in CF-relevant tissues in cftr^tm1Cam and cftr^{TgH(neoim)Hgu} mice and controls using real-time RT-qPCR.

Results

No consistent differences were observed except for mTTYH3 which was significantly down-regulated throughout the intestinal tract of cftr^tm1Cam mice.

Conclusions

Down-regulation of mTTYH3 may point towards its involvement in the complex CF pathology. However, the markedly reduced expression argues against a direct compensatory action as an alternative anion conductance. If any of the other candidates plays a role as modulator, factors other than transcriptional regulation and mRNA stability may be involved.