Posted 27 June 2010
Transgene: HuTau-tubulin kinase-1 (TTBK1) genomic DNA was isolated from RP3-330MP21
PAC DNA and after digestion the resultant 57kb fragment was injected into B6/SJL
F1 mouse blastocysts. Four founders were backcrossed to B6/129 F1.
Mutation: Overexpressing human Tau-tubulin kinase 1
Promoter: Endogenous human TTBK1 genomic promoter
Mouse strain: B6/129
TTBK1 mice develop age-dependent pathology in brain, including intraneuronal accumulation
of phosphorylated neurofiliment (p-NF), tau phosphorylation, cortical and hippocampal
astro/microgliois, calpain I upregulation, enhanced CDK5/p35/p25 and complex formation,
NMDA receptor down regulation, and memory impairment, all recapitulating the CDK5
activation-induced neuronal dysfunction in vivo.
In radial arm water maze test TTBK1-Tg mice show significant age-dependent memory
Dept. Pharmacology & Experimental Therapeutics, Boston University School of Medicine
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Sato S, Xu J, Okuyama S, Martinez LB, Walsh SM, Jacobsen MT, Swan RJ, Schlautman
JD, Ciborowski P, Ikezu T. Spatial learning impairment, enhanced CDK5/p35 activity,
and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin
kinase 1. J Neurosci. 2008 Dec 31;28(53):14511-21.
Xu J, Sato S, Okuyama S, Swan RJ, Jacobsen MT, Strunk E, Ikezu T. Tau-tubulin kinase
1 enhances prefibrillar tau aggregation and motor neuron degeneration in P301L FTDP-17
tau-mutant mice. FASEB J. 2010 Mar 30.