Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical consequences of a type II procollagen mutation that contained a Gly574Ser amino acid substitution were analyzed in a transgenic mouse strain. The mutation correlated with one previously characterized in a patient with the lethal human chondrodysplasia, hypochondrogenesis (Horton et al., 1992), and resulted in a similar shortlimbed phenotype. There were fewer collagen fibrils present in the transgenic cartilage and reduced immunofluorescence of cartilage matrix using a type II collagen antibody. Pepsin-extracted collagen from transgenic mouse embryo cartilage was analyzed electrophoretically and indicated less type II as well as type XI collagen compared to their wild-type littermates. A pulse-chase experiment was performed to evaluate the biosynthesis and fate of type II collagen. Chondrocytes isolated from transgenic tissue synthesized fewer stable molecules, resulting in decreased secretion of the procollagen chains. By amino acid sequence analysis of the type II collagen peptides from cartilage of transgenic mouse embryos, serine was not detected at residue 574, the site mutated in the transgene. Based on sequence data, we believe that the molecules incorporated into collagen fibrils of the extracellular matrix, while fewer in number, were composed of normal alpha 1(II) chains.
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PMID:Type II collagen pro-alpha-chains containing a Gly574Ser mutation are not incorporated into the cartilage matrix of transgenic mice. 931 59

Kniest dysplasia, a human chondrodysplasia that severely affects skeletal growth, is caused by mutations in the type II collagen gene, COL2A1. We report here on abnormal type II collagen in the cartilage from a lethal Kniest dysplasia case and identify a novel exon-skipping mutation. Screening of cyanogen bromide (CB) peptides from the cartilage samples by SDS-PAGE indicated an abnormality in peptide alpha1(II)CB11. Further peptide mapping and N-terminal sequence analysis showed a 15-amino-acid deletion encoded by exon 15 in about 25% of the alpha1(II) chains in the cartilage. The mutation responsible for exon skipping was found by sequencing amplified genomic DNA. The baby was heterozygous for a G to A transition at the first position of the splice donor of intron 15. Pepsin-solubilized type II collagen from the cartilage matrix contained both normal alpha1(II) and shortened chains expressed from the mutant allele. Trypsin cleaved the native molecules below 37 degrees C selectively at a site within the exon 15-encoded domain of the normal alpha1(II) chains. This is best explained by the coassembly of normal and truncated alpha1(II) chains into heterotrimers in which the triple helix is normally folded in both directions from the deletion site but the latter presents a region of local disruption. The findings support an emerging pattern of COL2A1 mutations that can cause Kniest dysplasia. Short deletions (single or partial exon) clustered in one region of the alpha1(II) chain are favored, resulting in abnormal heterotrimeric molecules that become a significant component of the cartilage extracellular matrix.
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PMID:Incorporation of structurally defective type II collagen into cartilage matrix in kniest chondrodysplasia. 967 39