title: Protein consequences of the Col2a1 C-propeptide mutation in the chondrodysplastic Dmm mouse.
abstract: The Disproportionate micromelia (Dmm) mouse has a three nucleotide deletion in Col2a1 in the region encoding the C-propeptide which results in the substitution of one amino acid, Asn, for two amino acids, Lys-Thr. Western blot and immunohistochemical analyses failed to detect type II collagen in the cartilage matrix of the homozygous mice and showed reduced levels in the matrix of heterozygous mice. Type II collagen chains localized intracellularly within the chondrocytes of homozygote and heterozygote tissues. These findings provide evidence that the expression of type II procollagen chains containing the defective C-propeptide results in an intracellular retention and faulty secretion of type II procollagen molecules. A complete absence of mature type II collagen from the homozygote cartilage and an insufficiency of type II collagen in the heterozygote cartilage explains the Dmm mouse phenotype. The integrity of the C-propeptide is thus crucial for the biosynthesis of normal type II collagen by chondrocytes.
authors: Orthopaedic Research Laboratories, Department of Orthopaedics and Sports Medicine, Box 356500, University of Washington, Seattle, WA 98195, USA. rjf@u.washington.edu
authors: Russell J
authors: RJ
authors: Fernandes
authors: Robert E
authors: RE
authors: Seegmiller
authors: Whitney R
authors: WR
authors: Nelson
authors: David R
authors: DR
authors: Eyre
mesh_terms: D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D002356:Cartilage / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D024043:Collagen Type II / Q000737:chemistry / Q000235:genetics*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D017434:Protein Structure, Tertiary
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D010455:Peptides; D003094:Collagen