Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms
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Abstract
COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent’s nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.
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SciScore for 10.1101/2021.03.29.437530: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Mice were euthanized by CO2 inhalation and the experimental procedures were in accordance with Swiss legislation and approved by the EXPANIM committee of the Lemanique Animal Facility Network and the veterinary authority of Canton de Vaud (SCAV). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication Authentication: Slices were then selected under a stereomicroscope (M165 FC; Leica) based on their general morphology and / or GFP expression. Table 2: Resources
Antibodies Sentences Resources The primary antibodies used were directed against ACE2 (Goat anti-ACE2; PA5-47488; … SciScore for 10.1101/2021.03.29.437530: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Mice were euthanized by CO2 inhalation and the experimental procedures were in accordance with Swiss legislation and approved by the EXPANIM committee of the Lemanique Animal Facility Network and the veterinary authority of Canton de Vaud (SCAV). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication Authentication: Slices were then selected under a stereomicroscope (M165 FC; Leica) based on their general morphology and / or GFP expression. Table 2: Resources
Antibodies Sentences Resources The primary antibodies used were directed against ACE2 (Goat anti-ACE2; PA5-47488; Invitrogen; 1:40), TMPRSS2 (Rabbit anti-TMPRSS2; ab109131; Abcam; 1:200), CK18 (Rabbit anti-CK18; PA5-14263; Invitrogen; 1:50), CK5 (Rabbit anti-CK5; ab52635; Abcam; 1:160), SOX2 (Rabbit anti-SOX2; PA1-094; Invitrogen; 1:200), GUST (Rabbit anti-Gα gust; sc-395; Santa Cruz Biotechnology; 1:250), S100B (Rabbit anti-S100β; ab41548; Abcam; 1:500), pGCG (Rabbit anti-PGCG; PGCG-701AP; FabGennix; 1:250) and γTUB (Rabbit anti-gamma Tubulin; ab179503; Abcam; 1:250). anti-ACE2suggested: (Thermo Fisher Scientific Cat# PA5-47488, RRID:AB_2606505)anti-TMPRSS2suggested: (Abcam Cat# ab109131, RRID:AB_10863728)CK18suggested: (Thermo Fisher Scientific Cat# PA5-14263, RRID:AB_2133178)anti-CK5suggested: NoneSOX2suggested: (Thermo Fisher Scientific Cat# PA1-094, RRID:AB_2539862)anti-SOX2; PA1-094suggested: (Thermo Fisher Scientific Cat# PA1-094, RRID:AB_2539862)anti-Gαsuggested: (Santa Cruz Biotechnology Cat# sc-393878, RRID:AB_2734138)S100Bsuggested: (Abcam Cat# ab41548, RRID:AB_956280)anti-S100βsuggested: Noneanti-PGCGsuggested: (Abcam Cat# ab41560, RRID:AB_777212)anti-gammasuggested: (LSBio (LifeSpan Cat# LS-B5281-250, RRID:AB_10914861)Detection of primary antibodies was performed using fluorochrome-conjugated secondary antibodies against goat (Alexa Fluor Plus 647-conjugated, donkey anti-Goat; A32849; Invitrogen; 1:200) and rabbit (Cy3-conjugated, donkey anti-Rabbit; 711-165-152; Jackson ImmunoResearch; 1:200). goat (Alexa Fluor Plus 647-conjugated, donkey anti-Goat; A32849suggested: Noneanti-Rabbitsuggested: (Jackson ImmunoResearch Labs Cat# 711-165-152, RRID:AB_2307443)Experimental Models: Organisms/Strains Sentences Resources Animals: C57BL/6 mice (Mus musculus; Janvier Labs) and heterozygote OMP-GFP mice39, of both sexes, were used at the indicated ages. OMP-GFPsuggested: NoneControl experiments were performed by omitting primary antibodies and ran in parallel on C57BL/6 mice. C57BL/6suggested: NoneResults 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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 22, 23, 26, 27, 28, 29 and 30. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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