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

Mette Camilla Kriegbaum; Benedikte Jacobsen; Annette Fuchtbauer; Gert Helge Hansen; Ib Jarle Christensen; Carsten Friis Rundsten; Morten Persson; Lars Henning Engelholm; Andreas Nygaard Madsen; Ivano Di Meo; Ida Katrine Lund; Birgitte Holst; Andreas Kjaer; Ole Didrik Laerum; Ernst-Martin Fuchtbauer; Michael Ploug

doi:10.1038/srep25833

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

Mette Camilla Kriegbaum, Benedikte Jacobsen, Annette Fuchtbauer, Gert Helge Hansen, Ib Jarle Christensen, Carsten Friis Rundsten, Morten Persson, Lars Henning Engelholm, Andreas Nygaard Madsen, Ivano Di Meo, Ida Katrine Lund, Birgitte Holst, Andreas Kjaer, Ole Didrik Laerum, Ernst-Martin Fuchtbauer, Michael Ploug

8 Citationer (Scopus)

Abstract

C4.4A is a modular glycolipid-anchored Ly6/uPAR/alpha-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.

Originalsprog	Engelsk
Artikelnummer	25833
Tidsskrift	Scientific Reports
Vol/bind	6
ISSN	2045-2322
DOI	https://doi.org/10.1038/srep25833
Status	Udgivet - 12 maj 2016

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10.1038/srep25833

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Kriegbaum, M. C., Jacobsen, B., Fuchtbauer, A., Hansen, G. H., Christensen, I. J., Rundsten, C. F., Persson, M., Engelholm, L. H., Madsen, A. N., Di Meo, I., Lund, I. K., Holst, B., Kjaer, A., Laerum, O. D., Fuchtbauer, E-M., & Ploug, M. (2016). C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes. Scientific Reports, 6, [25833]. https://doi.org/10.1038/srep25833

Kriegbaum, MC, Jacobsen, B, Fuchtbauer, A, Hansen, GH, Christensen, IJ, Rundsten, CF, Persson, M, Engelholm, LH, Madsen, AN, Di Meo, I, Lund, IK, Holst, B , Kjaer, A, Laerum, OD, Fuchtbauer, E-M & Ploug, M 2016, 'C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes', Scientific Reports, bind 6, 25833. https://doi.org/10.1038/srep25833

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

abstract = "C4.4A is a modular glycolipid-anchored Ly6/uPAR/alpha-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.",

author = "Kriegbaum, {Mette Camilla} and Benedikte Jacobsen and Annette Fuchtbauer and Hansen, {Gert Helge} and Christensen, {Ib Jarle} and Rundsten, {Carsten Friis} and Morten Persson and Engelholm, {Lars Henning} and Madsen, {Andreas Nygaard} and {Di Meo}, Ivano and Lund, {Ida Katrine} and Birgitte Holst and Andreas Kjaer and Laerum, {Ole Didrik} and Ernst-Martin Fuchtbauer and Michael Ploug",

year = "2016",

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doi = "10.1038/srep25833",

language = "English",

volume = "6",

journal = "Scientific Reports",

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T1 - C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes

AU - Kriegbaum, Mette Camilla

AU - Jacobsen, Benedikte

AU - Fuchtbauer, Annette

AU - Hansen, Gert Helge

AU - Christensen, Ib Jarle

AU - Rundsten, Carsten Friis

AU - Persson, Morten

AU - Engelholm, Lars Henning

AU - Madsen, Andreas Nygaard

AU - Di Meo, Ivano

AU - Lund, Ida Katrine

AU - Holst, Birgitte

AU - Kjaer, Andreas

AU - Laerum, Ole Didrik

AU - Fuchtbauer, Ernst-Martin

AU - Ploug, Michael

PY - 2016/5/12

Y1 - 2016/5/12

N2 - C4.4A is a modular glycolipid-anchored Ly6/uPAR/alpha-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.

AB - C4.4A is a modular glycolipid-anchored Ly6/uPAR/alpha-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.

U2 - 10.1038/srep25833

DO - 10.1038/srep25833

M3 - Journal article

C2 - 27169360

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 25833

ER -

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

Abstract

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