Posted 27 August 2005

General Information

Transgene: Crossed GSK3β^S9A with Tau4R to produce bigenic mice.

Mutation: Human GSK-3β (S9A) and human Tau

Promoter: Thy1

Mouse strain: FVB/N (Crl) for both transgenes

Phenotype

Neuropathological Analysis:

Human tg proteins expressed in neurons with high expression in cortex and hippocampus and lower expression in spinal cord. Hyperphosphorylation of tau in brain of bigenic mice at 4-6 weeks, but neither insoluble protein tau aggregates nor tangles were formed, not even at old age. Nearly compete rescue of the tau axonopathy (axonal dilations and motoric impairment) in bigenic tg mice concordant with disappearance of "swollen" axons (axonal dilatations are abundant in parental tau-4R mice).

Availability

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

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

Tilleman K, Van den Haute C, Geerts H, van Leuven F, Esmans EL, Moens L. Proteomics analysis of the neurodegeneration in the brain of tau transgenic mice.Proteomics. 2002 Jun;2(6):656-65. Abstract

Spittaels K, Van den Haute C, Van Dorpe J, Bruynseels K, Vandezande K, Laenen I, Geerts H, Mercken M, Sciot R, Van Lommel A, Loos R, Van Leuven F. Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein. Am J Pathol 1999 Dec;155(6):2153-65. Abstract