{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T14:54:22Z","timestamp":1763564062055,"version":"3.40.5"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["K08DC013556","R01DC016859"],"award-info":[{"award-number":["K08DC013556","R01DC016859"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Damage to olfactory sensory neurons (OSNs), situated within the neuroepithelium of the olfactory cleft, may be associated with anosmia. Although their direct contact with the nasal airspace make OSNs vulnerable to injury and death, multiple mechanisms maintain epithelium integrity and olfactory function. We hypothesized that BMI1, a polycomb protein found to be enriched in OSNs, may function in neuroprotection. Here, we explored BMI1 function in a mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Utilizing a mouse genetic approach to delete Bmi1 selectively in mature OSNs, we investigated changes in OE homeostasis by performing immunohistochemical, biochemical, and functional assays. Reverse transcription\u2013quantitative polymerase chain reaction (RT\u2010qPCR), immunostaining, and electro\u2010olfactograms were used to compare gene expression, cell composition, and olfactory function in OSN\u2010specific BMI1 knockout mice (n = 3 to 5) and controls. Chromatin studies were also performed to identify protein\u2010DNA interactions between BMI1 and its target genes (n = 3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OSN\u2010specific BMI1 knockout led to increased neuron death and basal cell activation. Chromatin studies suggested a mechanism of increased neurodegeneration due to de\u2010repression of a pro\u2010apoptosis gene, p19ARF. Despite the increased turnover, we found that olfactory neuroepithelium thickness and olfactory function remained intact. Our studies also revealed the presence of additional polycomb group proteins that may compensate for the loss of BMI1 in mature OSNs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The olfactory neuroepithelium employs multiple mechanisms to maintain epithelial homeostasis. Our findings provide evidence that in a mouse model of BMI1 deletion, the overall integrity and function of the olfactory neuroepithelium are not compromised, despite increased neuronal turnover, reflecting a remarkable reparative capacity to sustain a critical sensory system.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22366","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T20:07:01Z","timestamp":1561752421000},"page":"993-999","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Loss of BMI1 in mature olfactory sensory neurons leads to increased olfactory basal cell proliferation"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-9890","authenticated-orcid":false,"given":"Rhea","family":"Choi","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program, Miller School of Medicine University of Miami  Miami FL"},{"name":"Graduate Program in Neuroscience, Miller School of Medicine University of Miami  Miami FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Kurtenbach","sequence":"additional","affiliation":[{"name":"Interdisciplinary Stem Cell Institute, Miller School of Medicine University of Miami  Miami FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley J.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience, Miller School of Medicine University of Miami  Miami FL"},{"name":"Interdisciplinary Stem Cell Institute, Miller School of Medicine University of Miami  Miami FL"},{"name":"Department of Otolaryngology, Miller School of Medicine University of Miami  Miami FL"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/lio2.135"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2004.06.007"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1992.01880070061012"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1993.1201"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01175561"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1882"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19981102)400:4<469::AID-CNE3>3.0.CO;2-8"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22305"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199209000-00007"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7063870"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.142653"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5303-08.2009"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.549"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032015"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031870"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/lio2.180"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02433"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.333"},{"issue":"37","key":"e_1_2_6_20_1","first-page":"1850","article-title":"Analyzing responses of mouse olfactory sensory neurons using the air\u2010phase electroolfactogram recording","author":"Cygnar KD","year":"2010","journal-title":"J Vis Exp"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23653"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.097"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.065870"}],"container-title":["International Forum of Allergy &amp; 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