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/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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Kriegbaum MC,Jacobsen B,Füchtbauer A,Hansen GH,Christensen IJ,Rundsten CF,Persson M,Engelholm LH,Madsen AN,Di Meo I,Lund IK,Holst B,Kjaer A,Lærum OD,Füchtbauer EM,Ploug M

doi

10.1038/srep25833

subject

Has Abstract

pub_date

2016-05-12 00:00:00

pages

25833

issn

2045-2322

pii

srep25833

journal_volume

6

pub_type

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