{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T18:55:19Z","timestamp":1769972119450,"version":"3.49.0"},"reference-count":104,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,3,23]]},"abstract":"<jats:p>Here, we report on the analysis of keratin 18 null mice. Unlike the ablation of K8, which together with K18 is expressed in embryonic and simple adult epithelia, K18 null mice are viable, fertile, and show a normal lifespan. In young K18 null mice, hepatocytes were completely devoid of keratin filaments. Nevertheless, typical desmosomes were formed and maintained. Old K18 null mice, however, developed a distinctive liver pathology with abnormal hepatocytes containing K8-positive aggregates. These stained positively for ubiquitin and MM120-1 and were identified as Mallory bodies, one hallmark of human alcoholic hepatitis. This is the first demonstration that the ablation of one keratin leads to the accumulation of its single partner. Another striking finding was the absence or drastic down regulation of K7 in several tissues despite its ongoing transcription. Moreover, K18 null mice revealed new insights in the filament-forming capacity of the tail-less K19 in vivo. Due to the unexpected secondary loss of K7, only K8\/19 are expressed in the uterine epithelium of K18 null mice. Immunoelectron microscopy of this tissue demonstrated the presence of typical K8\/19 IF, thus highlighting in vivo that K19 is a fully competent partner for K8.<\/jats:p>","DOI":"10.1083\/jcb.140.6.1441","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:47:50Z","timestamp":1027702070000},"page":"1441-1451","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":189,"title":["Lessons from Keratin 18 Knockout Mice: Formation of Novel Keratin Filaments, Secondary Loss of Keratin 7 and Accumulation of Liver-specific Keratin 8-Positive Aggregates"],"prefix":"10.1083","volume":"140","author":[{"given":"Thomas M.","family":"Magin","sequence":"first","affiliation":[{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"},{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"},{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Leitgeb","sequence":"additional","affiliation":[{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederique","family":"Wanninger","sequence":"additional","affiliation":[{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Zatloukal","sequence":"additional","affiliation":[{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Grund","sequence":"additional","affiliation":[{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Melton","sequence":"additional","affiliation":[{"name":"*Institut fuer Genetik, Abteilung Molekulargenetik, \u2021Bonner Forum Biomedizin, \u00a7Neurologische Klinik und Poliklinik, Universitaet Bonn, 53117 Bonn, Germany; \u2016Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom; \u00b6Institut fuer Pathologie, Universitaet Graz, A-8036 Graz, Austria; **Abteilung fuer Zellbiologie, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1998,3,23]]},"reference":[{"key":"2023072207381156200_B1","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1083\/jcb.111.3.1197","article-title":"A single human keratin 18 gene is expressed in diverse epithelial cells of transgenic mice","volume":"111","author":"Abe","year":"1990","journal-title":"J Cell Biol"},{"key":"2023072207381156200_B2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1083\/jcb.105.2.791","article-title":"The expression of mutant epidermal keratin cDNAs transfected in simple epithelial and squamous cell carcinoma lines","volume":"105","author":"Albers","year":"1987","journal-title":"J Cell Biol"},{"key":"2023072207381156200_B3","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1083\/jcb.108.4.1477","article-title":"Expression of mutant keratin cDNAs in epithelial cells reveals possible mechanisms for initiation and assembly of intermediate filaments","volume":"108","author":"Albers","year":"1989","journal-title":"J Cell Biol"},{"key":"2023072207381156200_B4","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/j.1365-4362.1981.tb00815.x","article-title":"The structure and function of spot desmosomes","volume":"20","author":"Arnn","year":"1981","journal-title":"Int J Dermatol"},{"key":"2023072207381156200_B5","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1083\/jcb.115.5.1293","article-title":"Intermediate filaments formed de novo from tail-less cytokeratins in the cytoplasm and in the nucleus","volume":"115","author":"Bader","year":"1991","journal-title":"J Cell Biol"},{"key":"2023072207381156200_B6","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1002\/j.1460-2075.1986.tb04438.x","article-title":"Amino acid sequence and gene organization of cytokeratin no. 19, an exceptional tail-less intemediate filament protein","volume":"5","author":"Bader","year":"1986","journal-title":"EMBO (Eur Mol Biol Organ) J"},{"key":"2023072207381156200_B7","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1101\/gad.8.24.2964","article-title":"Colorectal hyperplasia and inflammation in keratin 8-deficient FVB\/N mice","volume":"8","author":"Baribault","year":"1994","journal-title":"Genes Dev"},{"key":"2023072207381156200_B8","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1101\/gad.7.7a.1191","article-title":"Mid-gestational lethality in mice lacking keratin 8","volume":"7","author":"Baribault","year":"1993","journal-title":"Genes Dev"},{"key":"2023072207381156200_B9","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/ijc.1985.36.3.299","article-title":"Patterns of expression of keratin 19 as detected with monoclonal antibodies in human breast tissues and tumours","volume":"36","author":"Bartek","year":"1985","journal-title":"Int J Cancer"},{"key":"2023072207381156200_B10","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1083\/jcb.120.3.743","article-title":"Ectopic synthesis of epidermal cytokeratins in pancreatic island cells of transgenic mice interferes with cytoskeletal order and insulin production","volume":"120","author":"Blessing","year":"1993","journal-title":"J Cell Biol"},{"key":"2023072207381156200_B11","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1126\/science.1720261","article-title":"Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities","volume":"2554","author":"Bonifas","year":"1991","journal-title":"Science"},{"key":"2023072207381156200_B12","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1242\/jcs.108.2.811","article-title":"Tissue-specific and efficient expression of the human simple epithelial keratin 8 gene in transgenic mice","volume":"108","author":"Casanova","year":"1995","journal-title":"J Cell Sci"},{"key":"2023072207381156200_B13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1242\/dev.101.3.565","article-title":"Cytokeratin filament assembly in the preimplantation mouse embryo","volume":"101","author":"Chisholm","year":"1987","journal-title":"Development"},{"key":"2023072207381156200_B14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal Biochem"},{"key":"2023072207381156200_B15","doi-asserted-by":"crossref","first-page":"4646","DOI":"10.1016\/S0021-9258(17)38550-2","article-title":"Monoclonal antibody analysis of bovine epithelial keratins. 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