Aspartoacylase gene, protein, and methods of screening for...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/55 (2006.01) A01K 67/027 (2006.01) A61K 38/50 (2006.01) A61K 48/00 (2006.01) C07H 21/00 (2006.01) C07K 16/40 (2006.01) C12N 1/21 (2006.01) C12N 5/10 (2006.01) C12N 9/80 (2006.01) C12N 15/63 (2006.01) C12P 21/02 (2006.01) C12Q 1/68 (2006.01) G01N 33/573 (2006.01)

Patent

CA 2172963

Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain. Human aspartoacylase (ASP) cDNA spanning 1,435 bp has been cloned and expressed in E. coli. A base change, a854>c, has been found in 85% of the 34 Canavan alleles tested so far, which results in a missense glu285>ala mutation that is predicted to be part of the catalytic domain of aspartoacylase. Several additional mutations have also been identified. The invention therefore provides nucleic acid sequences, genes, polypeptides, antibodies, vectors containing the gene, host cells transformed with vectors containing the gene, animal models for the disease, methods for expressing the polypeptide, genetic screening methods and kits, diagnostic methods and kits, methods of treating Canavan disease and methods of genetic therapy for the disease.

La maladie de Canavan, une leucodystrophie autosomique récessive, est causée par une déficience en aspartoacylase et l'accumulation d'acide N-acétylaspartique dans le cerveau. L'ADNc de l'aspartoacylase (ASP) humaine recouvrant 1 435 bp a été cloné et exprimé dans E.coli. Un changement de base, a854 > c, a été trouvé dans 85 % des 34 allèles de Canavan testés jusqu'ici, ladite modification ayant pour résultat une mutation faux sens glu285 > ala donnée comme faisant partie du domaine catalytique de l'aspartoacylase. Plusieurs autres mutations ont également été identifiées. L'invention concerne donc des séquences d'acide nucléique, des gènes, des polypeptides, des anticorps, des vecteurs contenant le gène, des cellules hôtes transformées avec des vecteurs contenant le gène, des modèles animaux relatifs à la maladie considérée, des procédés d'expression du polypeptide, des procédés et des trousses de criblage génétique, des procédés des trousses de diagnostic, des procédés de traitement de la maladie de Canavan et des procédés de thérapie génique relatifs à cette maladie.

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