title: Tgfbi/Bigh3 silencing activates ERK in mouse retina.
abstract: BIGH3 is a secreted protein, part of the extracellular matrix where it interacts with collagen and integrins on the cell surface. BIGH3 can play opposing roles in cancer, acting as either tumor suppressor or promoter, and its mutations lead to different forms of corneal dystrophy. Although many studies have been carried out, little is known about the physiological role of BIGH3. Using the cre-loxP system, we generated a mouse model with disruption of the Bigh3 genomic locus. Bigh3 silencing did not result in any apparent phenotype modifications, the mice remained viable and fertile. We were able to determine the presence of BIGH3 in the retinal pigment epithelium (RPE). In the absence of BIGH3, a transient decrease in the apoptotic process involved in retina maturation was observed, leading to a transient increase in the INL thickness at P15. This phenomenon was accompanied by an increased activity of the pro-survival ERK pathway.
authors.affiliation: Institut de Recherche en Ophtalmologie, Sion, Switzerland. Electronic address: nathalie.allaman-pillet@irovision.ch.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Allaman-Pillet
authors.affiliation: Institut de Recherche en Ophtalmologie, Sion, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Oberson
authors.affiliation: Institut de Recherche en Ophtalmologie, Sion, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bustamante
authors.affiliation: Institut de Recherche en Ophtalmologie, Sion, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tasinato
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Université de Lausanne, Lausanne, Switzerland.
authors.forename: Edith
authors.initials: E
authors.lastname: Hummler
authors.affiliation: Institut de Recherche en Ophtalmologie, Sion, Switzerland; Ecole polytechnique fédérale de Lausanne, Faculté des Sciences de la vie, Lausanne, Switzerland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D000818:Animals; D017209:Apoptosis; D015139:Blotting, Southern; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020868:Gene Silencing / Q000502:physiology*; D060005:Genotyping Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000201:enzymology* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D019938:Cyclin D1; D016326:Extracellular Matrix Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C530105:Ccnd1 protein, mouse
keywords: Apoptosis; BIGH3/TGFBI; Cornea; ERK; Retina