Posted 3 August 2010
Transgene: Amino acids 256-441 were removed from the longest human tau isoform,
htau40. The resulting cDNA was equipped with a human Kozak sequence and sub-cloned
into the XhoI site of mThy1.2 promotor vector for neuronal expression.
Mutation: ΔTau74
Promoter: Murine Thy1.2
Mouse strain: B6D2F1×B6D2F1. Background C57BL/6.
Neuropathological Analysis:
Developed 4 Δtau lines, line Δtau74 expresses transgene 1.4 fold higher
than endogenous tau. Found in hippocampus, cortex, and amygdala.
Δtau localizes to the soma, excluded from dendrites. Also expresses the projection
domain (PD) of tau in neurons.
Δtau74 lacks the MTB domain and therefore the MT-binding and aggregation properties
of full-length tau, but contains a Fyn binding site.
Δtau mice crossed with tau-/- (TauP301L) mice disrupt postsynaptic targeting
of Fyn. This uncouples NR-mediated excitotoxicity and hence mitigates Aβ toxicity.
Δtau expression and tau deficiency prevent memory deficits and improve survival
in Aβ-forming APP23 mice. These deficits are also fully rescued with a peptide
that uncouples the Fyn-mediated interaction of NR and PSD-95 in vivo.
Behavioral:
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:
Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng BC,
Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Götz J. Dendritic Function
of Tau Mediates Amyloid-beta Toxicity in Alzheimer's Disease Mouse Models. Cell.
2010 Jul 21. Abstract
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