title: A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis.
abstract: A missense mutation in the mouse Col2a1 gene has been discovered, resulting in a mouse phenotype with similarities to human spondyloepiphyseal dysplasia (SED) congenita. In addition, SED patients have been identified with a similar molecular mutation in human COL2A1. This mouse model offers a useful tool for molecular and biological studies of bone development and pathology.
  
  
  BACKGROUND
  A new mouse autosomal recessive mutation has been discovered and named spondyloepiphyseal dysplasia congenita (gene symbol sedc).
  
  
  METHODS
  Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora, and tibias, plus retinoschisis and hearing loss. The mutation was mapped to Chr15, and Col2a1 was identified as a candidate gene.
  
  
  RESULTS
  Sequence analyses revealed that the affected gene is Col2a1, which has a missense mutation at exon 48 causing an amino acid change of arginine to cysteine at position 1417. Two human patients with spondyloepiphyseal dysplasia (SED) congenita have been reported with the same amino acid substitution at position 789 in the human COL2A1 gene.
  
  
  CONCLUSIONS
  Thus, sedc/sedc mice provide a valuable model of human SED congenita with molecular and phenotypic homology. Further biochemical analyses, molecular modeling, and cell culture studies using sedc/sedc mice could provide insight into mechanisms of skeletal development dependent on Col2a1 and its role in fibril formation and cartilage template organization.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA. lrd@jax.org
authors.forename: Leah Rae
authors.initials: LR
authors.lastname: Donahue
authors.forename: Bo
authors.initials: B
authors.lastname: Chang
authors.forename: Subburaman
authors.initials: S
authors.lastname: Mohan
authors.forename: Nao
authors.initials: N
authors.lastname: Miyakoshi
authors.forename: Jon E
authors.initials: JE
authors.lastname: Wergedal
authors.forename: David J
authors.initials: DJ
authors.lastname: Baylink
authors.forename: Norman L
authors.initials: NL
authors.lastname: Hawes
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: Patricia
authors.initials: P
authors.lastname: Ward-Bailey
authors.forename: Qing Y
authors.initials: QY
authors.lastname: Zheng
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Johnson
authors.forename: Muriel T
authors.initials: MT
authors.lastname: Davisson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D024043:Collagen Type II / Q000235:genetics* / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005808:Genes, Recessive; D006132:Growth Plate / Q000002:abnormalities; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000151:congenital / Q000235:genetics*; D010641:Phenotype; D041441:Retinoschisis / Q000235:genetics*
chemical_list: C499177:COL2A1 protein, human; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D018076:DNA, Complementary