title: Collagen V is a dominant regulator of collagen fibrillogenesis: dysfunctional regulation of structure and function in a corneal-stroma-specific Col5a1-null mouse model.
abstract: Collagen V is a regulatory fibril-forming collagen that forms heterotypic fibrils with collagen I. Deletion of collagen V in the mouse is associated with a lack of fibril assembly in the embryonic mesenchyme, with a resultant lethal phenotype. The current work elucidates the regulatory roles of collagen V during development and growth of tissues. A conditional mouse model with a mutation in Col5a1 was developed using a Cre-loxP approach. Col5a1 was ablated in Col5a1(flox/flox) mice using a cornea stroma-specific Kera-Cre driver mouse to produce a bitransgenic Col5a1(Δst/Δst) line that is null for collagen V. This permits analyses of the corneal stroma, a widely used model for studies of collagen V. The collagen-V-knockout stroma demonstrated severe dysfunctional regulation of fibrillogenesis. Fibril diameters were significantly increased, with an abnormal, heterogeneous distribution; fibril structure was abnormal, fibril number was decreased and lamellae were disorganized with decreased stroma thickness. The phenotype was more severe in the anterior versus posterior stroma. Opacity was demonstrated throughout the Col5a1(Δst/Δst) stroma, with significantly increased haze intensity compared with control mice. These data indicate central regulatory roles for collagen V in fibril and matrix assembly during tissue development, with dysfunctional regulation resulting in a functional loss of transparency.
authors.affiliation: Department of Pathology and Cell Biology, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd, Tampa, FL 33612,  USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: Shoujun
authors.initials: S
authors.lastname: Chen
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Adams
authors.forename: Jane B
authors.initials: JB
authors.lastname: Florer
authors.forename: Hongshan
authors.initials: H
authors.lastname: Liu
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wenstrup
authors.forename: David E
authors.initials: DE
authors.lastname: Birk
mesh_terms: D000483:Alleles; D000818:Animals; D024062:Collagen Type V / Q000235:genetics / Q000378:metabolism*; D003318:Corneal Opacity / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010641:Phenotype
chemical_list: D024062:Collagen Type V