Pan-otic CRE drivers enable gene regulation throughout the otic placode lineage, comprising the inner ear epithelium and neurons. However, intersection of extra-otic gene-of-interest expression with the CRE lineage can compromise viability and impede auditory analyses. Furthermore, extant pan-otic CREs recombine in auditory and vestibular brain nuclei, making it difficult to ascribe resulting phenotypes solely to the inner ear. We previously identified Slc26a9 as an otic placode-specific target of FGFR2b ligands, FGF3 and FGF10. We show here that Slc26a9 is otic-specific through E10.5, but not required for hearing. We targeted P2ACre to the Slc26a9 stop codon, generating Slc26a9P2ACre mice, and observed CRE activity throughout the otic epithelium and neurons, with little activity evident in the brain. Notably, recombination was detected in many FGFR2b ligand-dependent epithelia. We generated Fgf10 and Fgf8 conditional mutants, and activated an FGFR2b ligand trap from E17.5-P3. In contrast to analogous mice generated with other pan-otic CREs, these were viable. Auditory thresholds were elevated in mutants, and correlated with cochlear epithelial cell losses. Thus, Slc26a9P2ACre provides a useful complement to existing pan-otic CRE drivers, particularly for postnatal analyses.

中文翻译：

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Slc26a9P2ACre，一种新的CRE驱动程序，可调节耳廓谱系和其他FGFR2b依赖的上皮细胞中的基因表达

Pan-otic CRE驱动程序可在整个耳道谱系中进行基因调节，包括内耳上皮和神经元。但是，外源目的基因表达与CRE谱系相交会损害生存能力并阻碍听觉分析。此外，现存的泛型CRE在听觉和前庭脑核中重组，因此很难将产生的表型仅归因于内耳。我们先前将Slc26a9确定为FGFR2b配体FGF3和FGF10的耳斑特定靶标。我们在这里显示Slc26a9通过E10.5具有耳部特异性，但不是听力所必需的。我们将P2ACre靶向Slc26a9终止密码子，生成Slc26a9P2ACre小鼠，并观察到整个耳上皮和神经元的CRE活性，而在大脑中几乎没有明显的活性。值得注意的是 在许多FGFR2b配体依赖性上皮细胞中检测到重组。我们生成了Fgf10和Fgf8条件突变体，并从E17.5-P3激活了FGFR2b配体陷阱。与其他泛型CRE产生的类似小鼠相反，它们是可行的。突变体的听觉阈值升高，并与耳蜗上皮细胞丢失相关。因此，Slc26a9P2ACre为现有的泛型CRE驱动程序提供了有用的补充，特别是对于产后分析。