Slc26a9P2ACre: A new CRE driver to regulate gene expression in the otic placode lineage and other FGFR2b-dependent epithelia

Lisa D. Urness, Xiaofen Wang, Chaoying Li, Rolen M. Quadros, Donald W. Harms, Channabasavaiah B. Gurumurthy, Suzanne L. Mansour

Research output: Contribution to journalArticle

Abstract

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 have previously identified Slc26a9 as an otic placode-specific target of the FGFR2b ligands FGF3 and FGF10. We show here that Slc26a9 is otic specific through E10.5, but is 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 to 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.

Original languageEnglish (US)
Article number191015
JournalDevelopment (Cambridge)
Volume147
Issue number13
DOIs
StatePublished - Jul 2020

Keywords

  • Cre driver
  • FGFR2b ligand trap
  • Fgf10 conditional mutant
  • Fgf8 conditional mutant
  • Hearing
  • Inner ear

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Slc26a9<sup>P2ACre</sup>: A new CRE driver to regulate gene expression in the otic placode lineage and other FGFR2b-dependent epithelia'. Together they form a unique fingerprint.

  • Cite this