title: Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen.
abstract: METHODS
  Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied.
  
  
  OBJECTIVE
  To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration.
  
  
  BACKGROUND
  Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown.
  
  
  METHODS
  Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice.
  
  
  RESULTS
  As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton.
  
  
  CONCLUSIONS
  Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.
authors.affiliation: Department of Anatomy, University of Kuopio, FIN-70211 Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Sahlman
authors.forename: R
authors.initials: R
authors.lastname: Inkinen
authors.forename: T
authors.initials: T
authors.lastname: Hirvonen
authors.forename: M J
authors.initials: MJ
authors.lastname: Lammi
authors.forename: P E
authors.initials: PE
authors.lastname: Lammi
authors.forename: J
authors.initials: J
authors.lastname: Nieminen
authors.forename: T
authors.initials: T
authors.lastname: Lapveteläinen
authors.forename: D J
authors.initials: DJ
authors.lastname: Prockop
authors.forename: M
authors.initials: M
authors.lastname: Arita
authors.forename: S W
authors.initials: SW
authors.lastname: Li
authors.forename: M M
authors.initials: MM
authors.lastname: Hyttinen
authors.forename: H J
authors.initials: HJ
authors.lastname: Helminen
authors.forename: K
authors.initials: K
authors.lastname: Puustjärvi
mesh_terms: D000375:Aging / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing / Q000502:physiology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006579:Heterozygote; D007403:Intervertebral Disc / Q000000981:diagnostic imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009043:Motor Activity; D009999:Ossification, Heterotopic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D011859:Radiography; D012016:Reference Values; D012886:Skull / Q000000981:diagnostic imaging; D013122:Spinal Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D013131:Spine / Q000000981:diagnostic imaging / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D006025:Glycosaminoglycans