Transgenic mammals expressing polyglutamine

Details Transgenic mammals expressing polyglutamine Transgenic mammals expressing polyglutamine

C - Chemistry, Metallurgy

12

Q

C12Q 1/00 (2006.01) A01K 67/027 (2006.01) G01N 33/00 (2006.01)

Patent

CA 2488932

The present invention utilizes a ~knock-in~ approach to provide a transgenic mammal containing integrated into its genome a repeating nucleotide sequence encoding a polyglutamine comprising at least about 154, preferably at least about 160, 200, 300, 400, 500, and up to 600 or more contiguous glutamine residues. The transgenic mammals normally display observable phenotypic changes. As such, they may serve as a model for disease processes in humans for such diseases as spinobulbar muscular atrophy (SBMA), Huntington's disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), and the spinocerebellar ataxias types, 1,2,3,6,7, and 17. As a result of displaying pathology indicative of a human disease, the efficacy of an agent for treating human disease may be tested in the transgenic mammals.

L'invention utilise une approche knock-in permettant de produire un animal transg~nique contenant, int~gr~ dans son g~nome, une s~quence nucl~otidique de r~p~tition codant pour une polyglutamine comprenant au moins environ 154, de pr~f~rence 160, 200, 300, 400, 500, et jusqu'~ 600 ou plus r~sidus contigus de glutamine. Les mammif­res transg~niques affichent normalement des changements ph~notypiques observables. En tant que tels, ces mammif­res peuvent servir de mod­le pour des processus pathologiques chez les humains dans le cas de maladies telles que l'atrophie musculaire spinobulbaire (SBMA), la maladie d'Huntington (HD), l'atrophie dentatorubrale et pallidoluysienne (DRPLA) et l'ataxie spinoc~r~brale de type 1,2,3,6,7, et 17. Le r~sultat de l'affichage d'une pathologie indicatrice d'une maladie humaine permet de tester chez les animaux transg~niques l'efficacit~ d'un agent destin~ ~ traiter une maladie humaine.

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