Transgene: C-alpha catalytic subunit of protein phosphatase (PP) 2A from human cDNA
Promoter: Neuron-specific mouse Thy1.2 promoter
Mouse Strain: B6D2F1 x B6D2F1
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.
Tg mice were overtly normal.
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.
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.