4.4 Article

Fate-mapping analysis using Rorb-IRES-Cre reveals apical-to-basal gradient of Rorb expression in mouse cochlea

期刊

DEVELOPMENTAL DYNAMICS
卷 249, 期 2, 页码 173-186

出版社

WILEY
DOI: 10.1002/dvdy.111

关键词

cochlea; hair cell; inner ear; Rorb; supporting cell

资金

  1. Ministry of Science and Technology of the People's Republic of China [2017YFA0103900, 2017YFA0103901]
  2. National Natural Science Foundation of China [81570919, 81771012]
  3. Shanghai Municipal Science and Technology Major Project [2018SHZDZX05]
  4. Strategic Priority Research Program of Chinese Academy of Science [XDB32000000]
  5. Boehringer Ingelheim (BI) International GmbH [DE811138149]

向作者/读者索取更多资源

Background Conditional loss-of-function studies are widely conducted using the Cre/Loxp system because this helps circumvent embryonic or neonatal lethality problems. However, Cre strains specific to the inner ear are lacking, and thus lethality frequently occurs even in conditional knockout studies. Results Here, we report a Rorb-IRES-Cre knockin mouse strain in which the Cre recapitulates the expression pattern of endogenous Rorb (RAR-related orphan receptor beta). Analysis of Rorb-IRES-Cre/+; Rosa26-CAG-LSL-tdTomato/+ cochlear samples revealed that tdTomato was expressed at the apical turn only by E12.5. TdTomato was observed in the apical and middle turns but was minimally expressed in the basal turn at E15.5, E18.5, and P5. However, most of the auditory hair cells (HCs) and supporting cells (SCs) in all three turns were tdTomato+ at P15 and P30. Intriguingly, no tdTomato+ vestibular cells were detected until P5 and a few cells were present at P15 and P30. Finally, we also confirmed Rorb mRNA and protein expression in cochlear HCs and SCs at P30. Conclusions We reveal that Rorb expression exhibits an apical-to-basal gradient in cochleae. The cochlear-specific and apical-to-basal-gradient Rorb Cre activity should enable discrimination of gene functions in cochlear vs vestibular regions as well as low-frequency vs high-frequency regions in the cochlea.

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