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

Mette Camilla Kriegbaum, Benedikte Jacobsen, Annette Füchtbauer, 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 L'rum, Ernst Martin Füchtbauer, Michael Ploug

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Abstract

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.

Original languageEnglish
Article number25833
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - May 12 2016

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Kriegbaum, M. C., Jacobsen, B., Füchtbauer, 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., L'rum, O. D., Füchtbauer, 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