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These include Bardet-Biedl syndrome (BBS), which is caused by mutations in BBS genes encoding for components of ciliary protein complexes essential for the assembly and maintenance of primary cilia. As in most ciliopathies, a hallmark feature of BBS is the development of cystic kidney disease. However, the molecular mechanisms linking ciliary dysfunction to cystogenesis remain incompletely understood. Here, we show that Bbs8\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice develop late-onset cystic kidney disease accompanied by increased regulated cell death and fibrosis. While the number and length of cilia are not affected, loss of BBS8 reduces K40 acetylation of \u03b1-tubulin within primary cilia, compromising ciliary stability. Notably, proteomic analysis revealed a significant upregulation of histone deacetylase HDAC2 in Bbs8\n                  <jats:sup>-\/-<\/jats:sup>\n                  kidneys, which we confirmed in Bbs8\n                  <jats:sup>-\/-<\/jats:sup>\n                  mouse embryonic fibroblasts (MEFs) and in urine-derived renal epithelial cells (URECs) from a BBS8 patient. We further demonstrate the protein interaction between BBS8 and HDAC2, implicating a disrupted BBS8\u2013HDAC2 regulatory axis in disease pathogenesis. Consistent with a role of excessive HDAC2 activity in the BBS8 deficient cells, pharmacological inhibition of HDAC2 restored tubulin acetylation in BBS8 urine-derived cells. Thus, modulation of HDAC2 activity may represent a strategy to alter ciliary stability in vivo which could explain positive effects of class I specific HDAC inhibitors in models of cystic kidney disease.\n                <\/jats:p>","DOI":"10.1101\/2024.03.07.583949","type":"posted-content","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T18:35:21Z","timestamp":1710268521000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of Bbs8 leads to cystic kidney disease in mice with reduced acetylation of ciliary alpha-tubulin through HDAC2"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7888-9185","authenticated-orcid":false,"given":"Emilia","family":"Kieckh\u00f6fer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2703-6680","authenticated-orcid":false,"given":"Julia","family":"G\u00fcnzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Matthiessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6583-3220","authenticated-orcid":false,"given":"Lena K.","family":"Ebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Klausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-6332","authenticated-orcid":false,"given":"Dagmar","family":"Wachten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-9204","authenticated-orcid":false,"given":"Metin","family":"Cetiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0494-9080","authenticated-orcid":false,"given":"Max C.","family":"Liebau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0512-1066","authenticated-orcid":false,"given":"Thomas","family":"Benzing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-4036","authenticated-orcid":false,"given":"Helen","family":"May-Simera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5194-9000","authenticated-orcid":false,"given":"Bernhard","family":"Schermer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025061908200957000_2024.03.07.583949v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"2025061908200957000_2024.03.07.583949v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"2025061908200957000_2024.03.07.583949v2.3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.36.6.437"},{"key":"2025061908200957000_2024.03.07.583949v2.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab039"},{"key":"2025061908200957000_2024.03.07.583949v2.5","doi-asserted-by":"publisher","DOI":"10.1093\/JMCB\/MJAD022"},{"key":"2025061908200957000_2024.03.07.583949v2.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911987106"},{"key":"2025061908200957000_2024.03.07.583949v2.7","doi-asserted-by":"crossref","unstructured":"Cognard, N. et al. 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