General Information

Transgene: C-alpha catalytic subunit of protein phosphatase (PP) 2A from human cDNA

Mutation: L199P

Promoter: Neuron-specific mouse Thy1.2 promoter

Mouse Strain: B6D2F1 x B6D2F1

Phenotype

Neuropathological Analysis:

Mutant PP2A subunit expressed in neuronal soma and dendrites in brain areas, including cortex, Purkinje cells of cerebellum, and in hippocampus.

Whole-brain homogenates of 5- and 12-month-old mice showed that overall PP2A phosphatase activity was reduced by 34% in Tg mice relative to wild type.

Tau hyperphosphorylation detected at AT8 epitope (Ser202/Thr205) and at Ser-422. AT8-immunoreactive tau aggregates found in axons, soma, and dendrites of cortical pyramidal cells and cerebellar Purkinje cells.

Most, but not all, AT8-positive tau aggregates colocalized with ubiquitin.

Behavioral:

Tg mice were overtly normal.

Availability

Patents:

References

Primary:

Kins S, Crameri A, Evans DRH, Hemmings BA, Nitsch RM, Gotz J. Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice. J Biol Chem. 12 Oct 2001;276(41):38193-2001. Abstract

Secondary:

Kins S, Kurosinski P, Nitsch RM, Götz J. Activation of the ERK and JNK signaling pathways caused by neuron-specific inhibition of PP2A in transgenic mice. Am J Pathol. 2003 Sep ; 163(3):833-43. Abstract