Madsen L.B., Bendixen Christian, Thomsen Bo.
2002. Identification of amino acid residues responsible for trimer association of the collagen X NC1 domain.
In : Second international symposium on Candidate Genes for Animal Health (C.G.A.H), Montpellier, France, August 16-18th 2002 : abstracts. CIRAD, INRA
Note générale : Session 4 : Genetic resistance / susceptibility to non-infectious diseases
Résumé : Schmid Metaphyseal Chondrodysplasia (SCMD) is an autosomal dominant disease associated with dwarfism and is caused by mutations clustered in the carboxyl-terminal non-collagenous domain (NC1) of collagen X. This domain is responsible for the initiation of trimerisation of collagen X during biosynthesis. The affected individuals show short stature with relatively short limbs, bowed legs, and a waddling gait. Until now 24 different mutations including deletions in the non collagenous domain (NC1) of the human collagen X are known to cause SCMD. The mutations causing SCMD are known to destabilise the NC1 trimer. In pigs, a mutation, G590R, in the porcine collagen X NC1 domain causes a phenotype that resembles SCMD. The porcine G590R mutation corresponds to the mutations G595R and G595E, which give rise to SCMD in humans. To evaluate the importance of the different amino acids for the NC1 trimerisation process, the porcine NC1 domain were mutated employing error prone PCR and the mutated constructs were tested in the yeast two hybrid system for their ability to interact with the wild type NC1 domain, and hence their ability to form trimers. Mutated constructs incapable of interacting with the wild type NC1 domain were subsequently sequenced and the responsible mutation was localised. Projecting the single mutations, which cause the lack of interaction, onto a crystal structure of the collagen X NC1 trimer reveals that the mutations can be grouped into three classes. One class contains amino acid residues situated in the core of the NC1 trimer. Another class contains residues placed in patches on the surface of the trimer and the third class contains amino acid residues located to the C-terminal of the NC1 domain. Some of the mutations causing the lack of association of the porcine NC1 domains have human analogues, known to cause SCMD in vivo. (Texte intégral)
Mots-clés Agrovoc : mutation, génétique moléculaire, acide aminé, maladie des animaux
Classification Agris : L10 - Génétique et amélioration des animaux
Auteurs et affiliations
- Madsen L.B., Danish Institute of Agricultural Sciences (DNK)
- Bendixen Christian, Danish Institute of Agricultural Sciences (DNK)
- Thomsen Bo, Danish Institute of Agricultural Sciences (DNK)
Autres liens de la publication
Source : Cirad - Agritrop (https://agritrop.cirad.fr/512116/)
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