Posted 13 June 2005

General Information

Transgene: cDNA coding for human GSK-3β (S9A) was ligated in the adapted mouse thy1 gene and was microinjected into 0.5-day-old FVB/N prenuclear mouse embryos.

Mutation: Human GSK-3β (S9A)

Promoter: Thy1

Mouse strain: FVB/N

Phenotype

Neuropathological Analysis:

Overexpressed in the CNS a constitutively active kinase resulting in a 2-fold increase of GSK-3β kinase activity. Human GSK-3β (S9A) hyperphosphorylates murine protein tau in the brain after 5-7 months. Rescue of the axonopathy in tau-4R x GSK-3β double tg mice

Availability

Licensing/academic distribution contact information:

Paul Van Dun
Director - KULeuvenR&D
Groot Begijnhof 59
B-3000 Leuven Belgium
tel +32 16 326508
fax +32 16 326515
Email: Paul.Vandun@lrd.kuleuven.ac.be
Web site: http://www.kuleuven.ac.be/lrd

Patents: none

References

Primary:

Spittaels K, Van den Haute C, Van Dorpe J, Geerts H, Mercken M, Bruynseels K, Lasrado R, Vandezande K, Laenen I, Boon T, Van Lint J, Vandenheede J, Moechars D, Loos R, Van Leuven F. Glycogen Synthase Kinase-3ß Phosphorylates Protein Tau and Rescues the Axonopathy in the Central Nervous System of Human Four-repeat Tau Transgenic Mice. J. Biol. Chem. 275(52): 41340-41349, 2000. Abstract.

Associated:

Spittaels K, Van den Haute C, Van Dorpe J, Terwel D, Vandezande K, Lasrado R, Bruynseels K, Irizarry M, Verhoye M, Van Lint J, Vandenheede JR, Ashton D, Mercken M, Loos R, Hyman B, Van der Linden A, Geerts H, Van Leuven F. Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice. Neuroscience. 2002;113(4):797-808. Abstract.

Nuydens R, Van Den Kieboom G, Nolten C, Verhulst C, Van Osta P, Spittaels K, Van den Haute C, De Feyter E, Geerts H, Van Leuven F. Coexpression of GSK-3beta corrects phenotypic aberrations of dorsal root ganglion cells, cultured from adult transgenic mice overexpressing human protein tau.Neurobiol Dis. 2002 Feb;9(1):38-48. Abstract.

Tilleman K, Stevens I, Spittaels K, Haute CV, Clerens S, Van Den Bergh G, Geerts H, Van Leuven F, Vandesande F, Moens L. Differential expression of brain proteins in glycogen synthase kinase-3 transgenic mice: a proteomics point of view.Proteomics. 2002 Jan;2(1):94-104. Abstract.