期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.761847
关键词
auditory brainstem response; degeneration; iDTR; neurofilament; spiral ganglion; Cre-LoxP
资金
- Veterans Affairs Merit Review Award
This study aimed to generate an SGN-specific damage model using Cre-LoxP transgenic mouse strains, successfully evaluating SGN cell loss through tamoxifen treatment and diphtheria toxin injection in mice. The Nefl (CreER/CreER) mouse strain exhibited inducible SGN-specific Cre activity in the inner ear, serving as a valuable model for regeneration research of the inner ear.
Spiral ganglion neurons (SGNs) can be injured by a wide variety of insults. However, there still is a lack of degeneration models to specifically damage the SGNs without disturbing other types of cells in the inner ear. This study aims to generate an SGN-specific damage model using the Cre-LoxP transgenic mouse strains. The Cre-inducible diphtheria toxin receptor (iDTR(+/+)) knock-in mouse strain was crossed with a mouse strain with Cre activity specific to neurons (Nefl(CreER/CreER)). Expression of the Cre-recombinase activity was evaluated using the reporter mouse strain Ai9 at pre-hearing, hearing onset, and post-hearing stages. Accordingly, heterozygous Nefl(CreER/+);iDTR(+/-) mice were treated with tamoxifen on postnatal days 1-5 (P1-5), followed by diphtheria toxin (DT) or vehicle injection on P7, P14, and P21 to evaluate the SGN loss. Robust tamoxifen-induced Cre-mediated Ai9 tdTomato fluorescence was observed in the SGN area of heterozygous Nefl(CreER/+);Ai9(+/-) mice treated with tamoxifen, whereas vehicle-treated heterozygote mice did not show tdTomato fluorescence. Compared to vehicle-treated Nefl(CreER/+);iDTR(+/-) mice, DT-treated Nefl(CreER/+);iDTR(+/-) mice showed significant auditory brainstem response (ABR) threshold shifts and SGN cell loss. Hair cell count and functional study did not show significant changes. These results demonstrate that the Nefl(CreER/CreER) mouse strain exhibits inducible SGN-specific Cre activity in the inner ear, which may serve as a valuable SGN damage model for regeneration research of the inner ear.
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