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/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.
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mette Camilla
authors.initials: MC
authors.lastname: Kriegbaum
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Benedikte
authors.initials: B
authors.lastname: Jacobsen
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Füchtbauer
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gert Helge
authors.initials: GH
authors.lastname: Hansen
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten Friis
authors.initials: CF
authors.lastname: Rundsten
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine &PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Persson
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars Henning
authors.initials: LH
authors.lastname: Engelholm
authors.affiliation: Deparment of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors.forename: Andreas Nygaard
authors.initials: AN
authors.lastname: Madsen
authors.affiliation: Unit of Molecular Neurogenetics, Foundation IRCCS Neurological Institute "Carlo Besta", Milano, Italy.
authors.forename: Ivano
authors.initials: I
authors.lastname: Di Meo
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ida Katrine
authors.initials: IK
authors.lastname: Lund
authors.affiliation: Deparment of Neuroscience and Pharmacology, University of Copenhagen, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Holst
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine &PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, The Gade Laboratory of Pathology, University of Bergen, Norway.
authors.forename: Ole Didrik
authors.initials: OD
authors.lastname: Lærum
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Ernst-Martin
authors.initials: EM
authors.lastname: Füchtbauer
authors.affiliation: The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Ploug
mesh_terms: D000818:Animals; D001835:Body Weight; D018827:Carcinoma, Lewis Lung; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D004848:Epithelium / Q000648:ultrastructure; D005260:Female; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008279:Magnetic Resonance Imaging; D008297:Male; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010641:Phenotype; D013347:Subcellular Fractions / Q000378:metabolism; D013851:Thinness / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D001743:Urinary Bladder / Q000473:pathology; D014870:Water Loss, Insensible; D014945:Wound Healing
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C557257:LYPD3 protein, mouse