title: Type XIV Collagen Regulates Fibrillogenesis: PREMATURE COLLAGEN FIBRIL GROWTH AND TISSUE DYSFUNCTION IN NULL MICE.
abstract: Type XIV collagen is a fibril-associated collagen with an interrupted triple helix. This collagen interacts with the fibril surface and has been implicated as a regulator of fibrillogenesis; however, a specific role has not been elucidated. Functional roles for type XIV collagen were defined utilizing a new type XIV collagen-deficient mouse line. This line was produced using a conventional targeted knock-out approach. Col14a1(-/-) mice were devoid of type XIV collagen, whereas heterozygous mice had reduced synthesis. Both mutant Col14a1 genotypes were viable with a grossly normal phenotype; however, mature skin exhibited altered mechanical properties. Prior to evaluating tendon fibrillogenesis in type XIV collagen-deficient mice, the developmental expression patterns were analyzed in wild-type flexor digitorum longus (FDL) tendons. Analyses of mRNA and protein expression indicated tissue-specific temporal expression that was associated with the early stages in fibrillogenesis. Ultrastructural analyses of wild-type and null tendons demonstrated premature fibril growth and larger fibril diameters in tendons from null mice at postnatal day 4 (P4). However, fibril structure in mature tendons was normal. Biomechanical studies established a direct structure/function relationship with reduced strength in P7-null tendons. However, the biomechanical properties in P60 tendons were comparable in null and wild-type mice. Our results indicate a regulatory function for type XIV collagen in early stages of collagen fibrillogenesis with tissue differences.
authors.affiliation: McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Ansorge
authors.forename: Xianmin
authors.initials: X
authors.lastname: Meng
authors.forename: Guiyun
authors.initials: G
authors.lastname: Zhang
authors.forename: Guido
authors.initials: G
authors.lastname: Veit
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: John F
authors.initials: JF
authors.lastname: Klement
authors.forename: David P
authors.initials: DP
authors.lastname: Beason
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Soslowsky
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
authors.forename: David E
authors.initials: DE
authors.lastname: Birk
mesh_terms: D000818:Animals; D003094:Collagen / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D006023:Glycoproteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D017433:Protein Structure, Secondary / Q000235:genetics; D012867:Skin / Q000378:metabolism* / Q000648:ultrastructure; D013710:Tendons / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C504563:Col14a1 protein, mouse; D006023:Glycoproteins; D003094:Collagen