Abnormal growth plate function in pigs carrying a dominant mutation in type X collagen

@article{Nielsen2000AbnormalGP,
  title={Abnormal growth plate function in pigs carrying a dominant mutation in type X collagen},
  author={Vivi H. Nielsen and Christian Bendixen and Jens Arnbjerg and Charlotte Mark S{\o}rensen and Henrik Elvang Jensen and Naseer M. Shukri and Bo Thomsen},
  journal={Mammalian Genome},
  year={2000},
  volume={11},
  pages={1087-1092}
}
Abstract. [...] Key Result Consistent with the clinical phenotype of SMCD patients, radiological and histological examination of the dwarf pigs revealed metaphyseal chondrodysplasia in the long bones. Yeast-based, two-hybrid protein interaction studies and in vitro assembly experiments demonstrated that the amino acid substitution interfered with the ability of the mutated collagen molecules to engage in trimerization. This work establishes that the chondrodysplastic dwarf pigs by genetic, biochemical…Expand
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TLDR
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TLDR
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A type X collagen mutation causes Schmid metaphyseal chondrodysplasia
TLDR
A 13 base pair deletion in one type X collagen allele segregating with autosomal dominant Schmid metaphyseal chondrodysplasia in a large Mormon kindred is identified, which may prevent association of the mutant polypeptide during trimer formation, resulting in a decreased amount of normal protein. Expand
Site-directed Mutagenesis of Human Type X Collagen
TLDR
Mutant type X collagen assembly was compromised in vivo, and mutant homotrimers formed in transiently transfected cells confirmed that the unassociated mutant chains were rapidly degraded. Expand
A nonsense mutation in the carboxyl-terminal domain of type X collagen causes haploinsufficiency in schmid metaphyseal chondrodysplasia.
TLDR
Analysis of the expression of the normal and mutant allele transcripts in growth plate cartilage demonstrated that only normal mRNA was present, and indicated that a functionally null allele leading to type X collagen haploinsufficiency is the molecular basis of SMCD in this patient. Expand
Type X Collagen Multimer Assembly in Vitro Is Prevented by a Gly618 to Val Mutation in the α1(X) NC1 Domain Resulting in Schmid Metaphyseal Chondrodysplasia (*)
TLDR
These studies provide the first evidence of the effect of a type X collagen mutation on protein structure and function and directly demonstrate the critical role of interactions between NC1 domains in the formation of typeX collagen multimeric structures in vitro. Expand
Phenotypic and biochemical consequences of collagen X mutations in mice and humans.
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This review focuses on how technological advances in murine transgenesis and human genetics are being used to address the role of collagen X, the major extracellular matrix component of the focal zone of endochondral ossification, the hypertrophic cartilage zone. Expand
Interaction of collagen alpha1(X) containing engineered NC1 mutations with normal alpha1(X) in vitro. Implications for the molecular basis of schmid metaphyseal chondrodysplasia.
TLDR
It is established that a conserved 13-amino acid aromatic motif (amino acids 589-601) is critical for the interaction between the NC1 domains, suggesting that this region may initiate assembly and the other NC1 mutations interfered with secondary interactions important in folding or in stabilizing the assembly process. Expand
Folding and Assembly of Type X Collagen Mutants That Cause Metaphyseal Chondrodysplasia-type Schmid
TLDR
It is demonstrated that although there is an apparent lower efficiency of association of the mutant NC1 domains, they can drive the formation of correctly aligned triple helices with the same thermal stability as the wild-type collagen. Expand
Molecular Genetics of the Human Chondrodysplasias — 1995
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Two loci, COL2A1 and FGFR3, account for most patients with chondrodysplasias — those with spondyloepiphyseal dysplasia and the achondroplasia classes of disorders, respectively. Expand
Abnormal Compartmentalization of Cartilage Matrix Components in Mice Lacking Collagen X: Implications for Function
TLDR
It is proposed that collagen X plays a role in the normal distribution of matrix vesicles and proteoglycans within the growth plate matrix, which would accommodate the previously conflicting views of the function of collagen X and of the molecular pathogenesis of SMCD. Expand
Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition
TLDR
It is reported here that mice carrying a mutated collagen X transgene develop skeletal deformities including compression of hypertrophic growth plate cartilage and a decrease in newly formed bone, as well as leukocyte deficiency in bone marrow, reduction in size of thymus and spleen, and lymphopenia. Expand
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