Posted 3 August 2010
Transgene: A 978bp cDNA of human PP2A C was fused to haemagglutinin (HA) epitope.
The L309A mutant introduced into cDNA. Neuron-specific mThy1.2 vector. Mice express
dominant negative mutant form.
Mutation: L309A
Promoter: Murine Thy1.2
Mouse strain: B6D2F1×B6D2F1. Background C57BL/6.
Neuropathological Analysis:
Strong expression of transgene in hippocampus and cortex. No neurological impairment
or neurodegeneration. Transgene expressed in brain areas affected by tau pathology
and neurodegeneration in AD.
When crossed with P301L (pR5) mice bigenic mice show 7-fold increase numbers of
hippocampal neurons that phosphorylate the pathological S422 epitope of tau. Also
8-fold increase numbers of tangles compared to pR5 mice.
Behavioral:
Normal size and fertility. No behavioral problems. Unaffected motor function on
rotarod. Delayed postnatal development and hypoplasia of the Harderian gland, causing
slit-eye phenotype (enophthalmos).
Lars Ittner or Jürgen Götz
Alzheimer’s and Parkinson’s Disease Lab, Brain and Mind Res. Institute
University of Sydney, Camperdown,, NSW 2050, Australia
Phone: +61-2-9351 0789 (or 0799)
Fax: +61-2-9351-0731
E-mail: Jürgen Götz (juergen.goetz@sydney.edu.au)
and Lars Ittner (lars.ittner@sydney.edu.au)
Patents: None
Primary:
Schild A, Isenmann S , Tanimoto N, Tonagel F, Seeliger MW, Ittner LM, Kretz A, Ogris
E, Götz J. Impaired development of the Harderian gland in mutant protein phosphatase
2A transgenic mice. Mech Dev. 2006 May;123(5):362-71.
Abstract
Associated:
van Eersel, J, Ke YD, Liu X, Kril J, Götz J, Ittner LM (2010) Sodium selenate treatment
mitigates tau pathology in Alzheimer’s disease models, Proc Natl Acad Sci U S A.
2010 Jul 19. Abstract
Deters N, Ittner LM, Götz J. Substrate-specific reduction of PP2A activity exaggerates
tau pathology. Biochem Biophys Res Commun. 2009 Feb 6;379(2):400-5.
Abstract
Schild A, Ittner L, Gotz J. Altered phosphorylation of cytoskeletal proteins in
mutant protein phosphatase 2A transgenic mice. Biochemical and Biophysical Res.
Communications 343, 1171-1178, 2006.
Abstract
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