Generation of a Spiral Ganglion Neuron Degeneration Mouse Model
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 tran...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.761847/full |
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| author | Zhengqing Hu Zhengqing Hu Fnu Komal Aditi Singh Meng Deng |
| author_facet | Zhengqing Hu Zhengqing Hu Fnu Komal Aditi Singh Meng Deng |
| author_sort | Zhengqing Hu |
| collection | DOAJ |
| description | 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 (NeflCreER/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 NeflCreER/+;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 NeflCreER/+;Ai9+/– mice treated with tamoxifen, whereas vehicle-treated heterozygote mice did not show tdTomato fluorescence. Compared to vehicle-treated NeflCreER/+;iDTR+/– mice, DT-treated NeflCreER/+;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 NeflCreER/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. |
| first_indexed | 2024-12-17T21:19:03Z |
| format | Article |
| id | doaj.art-0637f19250ed4b81b852502498b29d77 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-17T21:19:03Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-0637f19250ed4b81b852502498b29d772022-12-21T21:32:15ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-10-01910.3389/fcell.2021.761847761847Generation of a Spiral Ganglion Neuron Degeneration Mouse ModelZhengqing Hu0Zhengqing Hu1Fnu Komal2Aditi Singh3Meng Deng4John D. Dingell VA Medical Center, Detroit, MI, United StatesDepartment of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, MI, United StatesDepartment of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, MI, United StatesDepartment of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, MI, United StatesDepartment of Otolaryngology-HNS, Wayne State University School of Medicine, Detroit, MI, United StatesSpiral 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 (NeflCreER/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 NeflCreER/+;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 NeflCreER/+;Ai9+/– mice treated with tamoxifen, whereas vehicle-treated heterozygote mice did not show tdTomato fluorescence. Compared to vehicle-treated NeflCreER/+;iDTR+/– mice, DT-treated NeflCreER/+;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 NeflCreER/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.https://www.frontiersin.org/articles/10.3389/fcell.2021.761847/fullauditory brainstem responsedegenerationiDTRneurofilamentspiral ganglionCre-LoxP |
| spellingShingle | Zhengqing Hu Zhengqing Hu Fnu Komal Aditi Singh Meng Deng Generation of a Spiral Ganglion Neuron Degeneration Mouse Model Frontiers in Cell and Developmental Biology auditory brainstem response degeneration iDTR neurofilament spiral ganglion Cre-LoxP |
| title | Generation of a Spiral Ganglion Neuron Degeneration Mouse Model |
| title_full | Generation of a Spiral Ganglion Neuron Degeneration Mouse Model |
| title_fullStr | Generation of a Spiral Ganglion Neuron Degeneration Mouse Model |
| title_full_unstemmed | Generation of a Spiral Ganglion Neuron Degeneration Mouse Model |
| title_short | Generation of a Spiral Ganglion Neuron Degeneration Mouse Model |
| title_sort | generation of a spiral ganglion neuron degeneration mouse model |
| topic | auditory brainstem response degeneration iDTR neurofilament spiral ganglion Cre-LoxP |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.761847/full |
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