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
Neuropathological Analysis:
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.
Behavioral:
In radial arm water maze test TTBK1-Tg mice show significant age-dependent memory impairment.
Tsuneya Ikezu
Dept. Pharmacology & Experimental Therapeutics, Boston University School of Medicine
TTBK1
72 East Concord Street, L-606, Boston, MA 02118
Phone: (617) 414-2658
Fax: (617) 638-4329
E-mail: tikezu@bu.edu
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UNeMed Corporation
Annex 14
4460 Farnam Street, Room 3000
Omaha, NE 68131-2729
Phone: (402) 559-2468
www.unemed.com
Patents: none
Primary:
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. Abstract
Associated:
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. Abstract
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