Expression of ACE2 , TMPRSS2 , and Furin in Mouse Ear Tissue, and the Implications for SARS‐CoV ‐2 Infection

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Abstract

Intracellular entry of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) depends on the interaction between its spike protein with the cellular receptor angiotensin‐converting enzyme 2 (ACE2) and depends on Furin‐mediated spike protein cleavage and spike protein priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). As the expression of ACE2, TMPRSS2, and Furin in the middle and inner ear remain unclear, we analyzed the expression of these proteins in mouse ear tissues.

Study Design

Animal Research.

Methods

We performed immunohistochemical analysis to examine the distribution of ACE2, TMPRSS2, and Furin in the Eustachian tube, middle ear spaces, and cochlea of mice.

Results

ACE2 was present in the nucleus of the epithelium of the middle ear and Eustachian tube, as well as in some nuclei of the hair cells in the organ of Corti, in the stria vascularis, and the spiral ganglion cells. ACE2 was also expressed in the cytoplasm of the stria vascularis. TMPRSS2 was expressed in both the nucleus and cytoplasm in the middle spaces, with the expression being stronger in the nucleus in the mucosal epithelium of the middle ear spaces and Eustachian tube. TMPRSS2 was present in the cytoplasm in the organ of Corti and stria vascularis and in the nucleus and cytoplasm in the spiral ganglion. Furin was expressed in the cytoplasm in the middle ear spaces, Eustachian tube, and cochlea.

Conclusions

ACE2, TMPRSS2, and Furin are diffusely present in the Eustachian tube, middle ear spaces, and cochlea, suggesting that these tissues are susceptible to SARS‐CoV‐2 infection.

Level of Evidence

NA Laryngoscope , 131:E2013–E2017, 2021

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  1. SciScore for 10.1101/2020.06.23.164335: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All experiments were conducted in accordance with institutional guidelines and with the approval of the Animal Care and Use Committee of the University of Tokyo (No. P18-015) Histological analyses: Immunohistochemical staining was performed for Ace2 and Tmprss2.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableTissue samples were obtained from normal 11-week-old male ICR mice, and paraffin-embedded tissue samples including the middle ear spaces, Eustachian tube area, and cochlea were used (Figure 1, 2).

    Table 2: Resources

    Antibodies
    SentencesResources
    dilution; rabbit monoclonal, Abcam, ab92323; Cambridge, UK), and anti-Furin (1:100
    anti-Furin
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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