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C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes

C4.4A is a modular glycolipid-anchored Ly6/uPAR/α-neurotoxin multidomain protein that exhibits a prominent membrane-associated expression in stratified squamous epithelia. C4.4A is also expressed in various solid cancer lesions, where high expression levels often are correlated to poor prognosis. Ci...

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Autores principales: Kriegbaum, Mette Camilla, Jacobsen, Benedikte, Füchtbauer, Annette, Hansen, Gert Helge, Christensen, Ib Jarle, Rundsten, Carsten Friis, Persson, Morten, Engelholm, Lars Henning, Madsen, Andreas Nygaard, Di Meo, Ivano, Lund, Ida Katrine, Holst, Birgitte, Kjaer, Andreas, Lærum, Ole Didrik, Füchtbauer, Ernst-Martin, Ploug, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864438/
https://www.ncbi.nlm.nih.gov/pubmed/27169360
http://dx.doi.org/10.1038/srep25833
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author Kriegbaum, Mette Camilla
Jacobsen, Benedikte
Füchtbauer, Annette
Hansen, Gert Helge
Christensen, Ib Jarle
Rundsten, Carsten Friis
Persson, Morten
Engelholm, Lars Henning
Madsen, Andreas Nygaard
Di Meo, Ivano
Lund, Ida Katrine
Holst, Birgitte
Kjaer, Andreas
Lærum, Ole Didrik
Füchtbauer, Ernst-Martin
Ploug, Michael
author_facet Kriegbaum, Mette Camilla
Jacobsen, Benedikte
Füchtbauer, Annette
Hansen, Gert Helge
Christensen, Ib Jarle
Rundsten, Carsten Friis
Persson, Morten
Engelholm, Lars Henning
Madsen, Andreas Nygaard
Di Meo, Ivano
Lund, Ida Katrine
Holst, Birgitte
Kjaer, Andreas
Lærum, Ole Didrik
Füchtbauer, Ernst-Martin
Ploug, Michael
author_sort Kriegbaum, Mette Camilla
collection PubMed
description C4.4A is a modular glycolipid-anchored Ly6/uPAR/α-neurotoxin multidomain protein that exhibits a prominent membrane-associated expression in stratified squamous epithelia. C4.4A is also expressed in various solid cancer lesions, where high expression levels often are correlated to poor prognosis. Circumstantial evidence suggests a role for C4.4A in cell adhesion, migration, and invasion, but a well-defined biological function is currently unknown. In the present study, we have generated and characterized the first C4.4A-deficient mouse line to gain insight into the functional significance of C4.4A in normal physiology and cancer progression. The unchallenged C4.4A-deficient mice were viable, fertile, born in a normal Mendelian distribution and, surprisingly, displayed normal development of squamous epithelia. The C4.4A-deficient mice were, nonetheless, significantly lighter than littermate controls predominantly due to differences in fat mass. Congenital C4.4A deficiency delayed migration of keratinocytes enclosing incisional skin wounds in male mice. In chemically induced bladder carcinomas, C4.4A deficiency attenuated the incidence of invasive lesions despite having no effect on total tumour burden. This new C4.4A-deficient mouse line provides a useful platform for future studies on functional aspects of C4.4A in tumour cell invasion in vivo.
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spelling pubmed-48644382016-05-23 C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes Kriegbaum, Mette Camilla Jacobsen, Benedikte Füchtbauer, Annette Hansen, Gert Helge Christensen, Ib Jarle Rundsten, Carsten Friis Persson, Morten Engelholm, Lars Henning Madsen, Andreas Nygaard Di Meo, Ivano Lund, Ida Katrine Holst, Birgitte Kjaer, Andreas Lærum, Ole Didrik Füchtbauer, Ernst-Martin Ploug, Michael Sci Rep Article C4.4A is a modular glycolipid-anchored Ly6/uPAR/α-neurotoxin multidomain protein that exhibits a prominent membrane-associated expression in stratified squamous epithelia. C4.4A is also expressed in various solid cancer lesions, where high expression levels often are correlated to poor prognosis. Circumstantial evidence suggests a role for C4.4A in cell adhesion, migration, and invasion, but a well-defined biological function is currently unknown. In the present study, we have generated and characterized the first C4.4A-deficient mouse line to gain insight into the functional significance of C4.4A in normal physiology and cancer progression. The unchallenged C4.4A-deficient mice were viable, fertile, born in a normal Mendelian distribution and, surprisingly, displayed normal development of squamous epithelia. The C4.4A-deficient mice were, nonetheless, significantly lighter than littermate controls predominantly due to differences in fat mass. Congenital C4.4A deficiency delayed migration of keratinocytes enclosing incisional skin wounds in male mice. In chemically induced bladder carcinomas, C4.4A deficiency attenuated the incidence of invasive lesions despite having no effect on total tumour burden. This new C4.4A-deficient mouse line provides a useful platform for future studies on functional aspects of C4.4A in tumour cell invasion in vivo. Nature Publishing Group 2016-05-12 /pmc/articles/PMC4864438/ /pubmed/27169360 http://dx.doi.org/10.1038/srep25833 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kriegbaum, Mette Camilla
Jacobsen, Benedikte
Füchtbauer, Annette
Hansen, Gert Helge
Christensen, Ib Jarle
Rundsten, Carsten Friis
Persson, Morten
Engelholm, Lars Henning
Madsen, Andreas Nygaard
Di Meo, Ivano
Lund, Ida Katrine
Holst, Birgitte
Kjaer, Andreas
Lærum, Ole Didrik
Füchtbauer, Ernst-Martin
Ploug, Michael
C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
title C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
title_full C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
title_fullStr C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
title_full_unstemmed C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
title_short C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
title_sort c4.4a gene ablation is compatible with normal epidermal development and causes modest overt phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864438/
https://www.ncbi.nlm.nih.gov/pubmed/27169360
http://dx.doi.org/10.1038/srep25833
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