Linked Life Data

21538020

Source:http://linkedlifedata.com/resource/pubmed/id/21538020

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2011-5-23
pubmed:abstractText
The COL2A1 gene encodes the ?1(II) chain of the homotrimeric type II collagen, the most abundant protein in cartilage. In humans, COL2A1 mutations create many clinical phenotypes collectively termed type II collagenopathies; however, the genetic basis of the phenotypic diversity is not well elucidated. Therefore, animal models corresponding to multiple type II collagenopathies are required. In this study we identified a novel Col2a1 missense mutation--c.44406A>C (p.D1469A)--produced by large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis in a mouse line. This mutation was located in the C-propeptide coding region of Col2a1 and in the positions corresponding to a human COL2A1 mutation responsible for platyspondylic lethal skeletal dysplasia, Torrance type (PLSD-T). The phenotype was inherited as a semidominant trait. The heterozygotes were mildly but significantly smaller than wild-type mice. The homozygotes exhibited lethal skeletal dysplasias, including extremely short limbs, severe spondylar dysplasia, severe pelvic hypoplasia, and brachydactyly. As expected, these skeletal defects in the homozygotes were similar to those in PLSD-T patients. The secretion of the mutant proteins into the extracellular space was disrupted, accompanied by abnormally expanded rough endoplasmic reticulum (ER) and upregulation of ER stress-related genes, such as Grp94 and Chop, in chondrocytes. These findings suggested that the accumulation of mutant type II collagen in the ER and subsequent induction of ER stress are involved, at least in part in the PLSD-T-like phenotypes of the mutants. This mutant should serve as a good model for studying PLSD-T pathogenesis and the mechanisms that create the great diversity of type II collagenopathies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1432-1777
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
318-28
pubmed:meshHeading
pubmed-meshheading:21538020-Alcian Blue, pubmed-meshheading:21538020-Animals, pubmed-meshheading:21538020-Anthraquinones, pubmed-meshheading:21538020-Bone and Bones, pubmed-meshheading:21538020-Chromosome Mapping, pubmed-meshheading:21538020-Collagen Type II, pubmed-meshheading:21538020-DNA Primers, pubmed-meshheading:21538020-Disease Models, Animal, pubmed-meshheading:21538020-Ethylnitrosourea, pubmed-meshheading:21538020-Genotype, pubmed-meshheading:21538020-Immunohistochemistry, pubmed-meshheading:21538020-Mice, pubmed-meshheading:21538020-Mice, Mutant Strains, pubmed-meshheading:21538020-Microscopy, Electron, Transmission, pubmed-meshheading:21538020-Mutagenesis, pubmed-meshheading:21538020-Mutation, Missense, pubmed-meshheading:21538020-Osteochondrodysplasias, pubmed-meshheading:21538020-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2011
pubmed:articleTitle
ENU-induced missense mutation in the C-propeptide coding region of Col2a1 creates a mouse model of platyspondylic lethal skeletal dysplasia, Torrance type.
pubmed:affiliation
Laboratory Animal Facility, Research Center for Medical Sciences, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. furuichi@jikei.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't