Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice
Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar les...
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| creator | Sundberg, John P Pratt, C Herbert Goodwin, Leslie P Silva, Kathleen A Kennedy, Victoria E Potter, Christopher S Dunham, Anisa Sundberg, Beth A HogenEsch, Harm |
| description | Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis. |
| doi_str_mv | 10.1371/journal.pone.0235295 |
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To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0235295</identifier><identifier>PMID: 32687504</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis ; Apoptosis - genetics ; Arthritis ; Arthritis - genetics ; Arthritis - pathology ; Atopic dermatitis ; Biology and Life Sciences ; Cell culture ; Defects ; Dendritic cells ; Dermatitis ; Dermatitis, Atopic - genetics ; Dermatitis, Atopic - pathology ; Disease ; Disease Models, Animal ; Eczema ; Fibroblasts ; Gene deletion ; Gene Expression Regulation - genetics ; Genotype & phenotype ; Humans ; Immunoglobulin E ; Immunoglobulin E - genetics ; Inflammation ; Inflammation - genetics ; Inflammation - pathology ; Integrases - genetics ; Interleukin 1 ; Interleukin 18 ; Interleukin-18 - genetics ; Keratin-14 - genetics ; Keratinocytes ; Keratinocytes - metabolism ; Keratinocytes - pathology ; Laboratory animals ; Lesions ; Leukocytes (eosinophilic) ; Medicine and Health Sciences ; Mice ; Mutants ; Mutation ; Nerve Tissue Proteins - genetics ; NF-kappa B - genetics ; NF-κB protein ; Organs ; Phenotype ; Phenotypes ; Physiological aspects ; Proteins ; Recombinase ; Research and Analysis Methods ; Rodents ; S100 Calcium-Binding Protein A4 - genetics ; S100A4 protein ; Signal Transduction ; Skin diseases ; Skin lesions ; Veterinary colleges ; Veterinary medicine</subject><ispartof>PloS one, 2020-07, Vol.15 (7), p.e0235295</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Sundberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Sundberg et al 2020 Sundberg et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-cc4bcb2b9640c83c7d20b3bbe2cf27864716384eebb5b9592fcb12a82747ba7b3</citedby><cites>FETCH-LOGICAL-c692t-cc4bcb2b9640c83c7d20b3bbe2cf27864716384eebb5b9592fcb12a82747ba7b3</cites><orcidid>0000-0002-1523-5430 ; 0000-0002-4261-0750 ; 0000-0003-1868-5055</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371178/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371178/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32687504$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Simon, Michel</contributor><creatorcontrib>Sundberg, John P</creatorcontrib><creatorcontrib>Pratt, C Herbert</creatorcontrib><creatorcontrib>Goodwin, Leslie P</creatorcontrib><creatorcontrib>Silva, Kathleen A</creatorcontrib><creatorcontrib>Kennedy, Victoria E</creatorcontrib><creatorcontrib>Potter, Christopher S</creatorcontrib><creatorcontrib>Dunham, Anisa</creatorcontrib><creatorcontrib>Sundberg, Beth A</creatorcontrib><creatorcontrib>HogenEsch, Harm</creatorcontrib><title>Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. 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This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Arthritis</subject><subject>Arthritis - genetics</subject><subject>Arthritis - pathology</subject><subject>Atopic dermatitis</subject><subject>Biology and Life Sciences</subject><subject>Cell culture</subject><subject>Defects</subject><subject>Dendritic cells</subject><subject>Dermatitis</subject><subject>Dermatitis, Atopic - genetics</subject><subject>Dermatitis, Atopic - pathology</subject><subject>Disease</subject><subject>Disease Models, Animal</subject><subject>Eczema</subject><subject>Fibroblasts</subject><subject>Gene deletion</subject><subject>Gene Expression Regulation - genetics</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Immunoglobulin E</subject><subject>Immunoglobulin E - 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genetics</subject><subject>S100A4 protein</subject><subject>Signal Transduction</subject><subject>Skin diseases</subject><subject>Skin lesions</subject><subject>Veterinary colleges</subject><subject>Veterinary medicine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk81u1DAUhSMEoqXwBggiISFYZHBsJ3Y2lUYV0BEVRS2wQ5bt3My4OPEQO4i-PU4nrSaoC5RFouvvnBvfnyR5nqNFTlj-7soNfSftYus6WCBMClwVD5LDvCI4KzEiD_e-D5In3l8hVBBelo-TA4JLzgpED5Mfn6CXwXROXwfI_Ba0aYxOa7AQjOtS16SXp8uLL6vPqenqQYNPZXDbG6RvozIYn1nzE-JxY2U7hqLMdGlrNDxNHjXSeng2vY-Sbx_efz05zc7OP65OlmeZLiscMq2p0gqrqqRIc6JZjZEiSgHWDWa8pCwvCacAShWqKircaJVjyTGjTEmmyFHycue7tc6LqTJeYIqLglNSFJFY7YjaySux7U0r-2vhpBE3AdevheyD0RYErjQljeKVVEBrxHgTDRqKakqBSTR6HU_ZBtVCraELvbQz0_lJZzZi7X4LFvuWMx4N3kwGvfs1gA-iNV6DtbIDN-z-m1dFno-5Xv2D3n-7iVrLeIHYCRfz6tFULEuCEMa8rCK1uIeKTw2xWXGMGhPjM8HbmSAyAf6EtRy8F6vLi_9nz7_P2dd77AakDRvv7DCOjp-DdAfq3nnfQ3NX5ByJcQtuqyHGLRDTFkTZi_0G3Ylux578BXncAj4</recordid><startdate>20200720</startdate><enddate>20200720</enddate><creator>Sundberg, John P</creator><creator>Pratt, C Herbert</creator><creator>Goodwin, Leslie P</creator><creator>Silva, Kathleen A</creator><creator>Kennedy, Victoria E</creator><creator>Potter, Christopher S</creator><creator>Dunham, Anisa</creator><creator>Sundberg, Beth A</creator><creator>HogenEsch, Harm</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1523-5430</orcidid><orcidid>https://orcid.org/0000-0002-4261-0750</orcidid><orcidid>https://orcid.org/0000-0003-1868-5055</orcidid></search><sort><creationdate>20200720</creationdate><title>Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice</title><author>Sundberg, John P ; Pratt, C Herbert ; Goodwin, Leslie P ; Silva, Kathleen A ; Kennedy, Victoria E ; Potter, Christopher S ; Dunham, Anisa ; Sundberg, Beth A ; HogenEsch, Harm</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-cc4bcb2b9640c83c7d20b3bbe2cf27864716384eebb5b9592fcb12a82747ba7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - 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To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. 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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis Apoptosis - genetics Arthritis Arthritis - genetics Arthritis - pathology Atopic dermatitis Biology and Life Sciences Cell culture Defects Dendritic cells Dermatitis Dermatitis, Atopic - genetics Dermatitis, Atopic - pathology Disease Disease Models, Animal Eczema Fibroblasts Gene deletion Gene Expression Regulation - genetics Genotype & phenotype Humans Immunoglobulin E Immunoglobulin E - genetics Inflammation Inflammation - genetics Inflammation - pathology Integrases - genetics Interleukin 1 Interleukin 18 Interleukin-18 - genetics Keratin-14 - genetics Keratinocytes Keratinocytes - metabolism Keratinocytes - pathology Laboratory animals Lesions Leukocytes (eosinophilic) Medicine and Health Sciences Mice Mutants Mutation Nerve Tissue Proteins - genetics NF-kappa B - genetics NF-κB protein Organs Phenotype Phenotypes Physiological aspects Proteins Recombinase Research and Analysis Methods Rodents S100 Calcium-Binding Protein A4 - genetics S100A4 protein Signal Transduction Skin diseases Skin lesions Veterinary colleges Veterinary medicine |
| title | Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T13%3A29%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Keratinocyte-specific%20deletion%20of%20SHARPIN%20induces%20atopic%20dermatitis-like%20inflammation%20in%20mice&rft.jtitle=PloS%20one&rft.au=Sundberg,%20John%20P&rft.date=2020-07-20&rft.volume=15&rft.issue=7&rft.spage=e0235295&rft.pages=e0235295-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0235295&rft_dat=%3Cgale_plos_%3EA630022869%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2425584355&rft_id=info:pmid/32687504&rft_galeid=A630022869&rft_doaj_id=oai_doaj_org_article_29c43fb89abe4d078f355f40d44e7a05&rfr_iscdi=true |