Updated 9 March 2010
TARDBP (NM_007375) was amplified from a human cDNA library (hTDP-43) and
cloned into an mTUB expression vector containing a murine Thy-1 promoter. The expression
vector was microinjected into pronuclear oocytes of Bl6/SJL mice. Founders were
bred with C57Bl6/J mice.
Mutation: Overexpressing hTDP-43.
Promoter: Murine Thy-1 promoter.
Mouse strain: C57Bl6/J. Background strain: Bl6/SJL. Current Generation Number: ˜F4.
Colony maintenance: Homozygous hTDP-43-overexpressing mice were generated for two
selected lines by crossbreeding hemizygous hTDP-43-overexpressing mice.
Neuropathological analysis:
Overexpression of WT TDP-43 leads to degeneration of specific neurons in the central
nervous system, including spinal and cortical motor neurons and non-motor cortical
neurons characteristically affected in FTLD-TDP, and causes spastic quadriplegia
in a dose-dependent manner (ALS).
Behavioral Phenotype:
Abnormal limb reflex seen in highest expressing homozygous mice at ~ 14 days characterized
by retraction of hindlegs toward the trunk upon lifting them by their tail. At 18
days mice show poor motor performance on accelerating rotarod. At ~22 days, fasciculations
and spasms of facial muscles were observed, followed by an extremely rapid disease
progression, with mice becoming completely paralyzed and dying within 3–4 days.
Contact: Samir Kumar-Singh
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB
University of Antwerp (CDE), B-2610 Antwerpen, Belgium
Telephone: +32 3 265 1002
Fax: +32 3 265 1012
Samir Kumar-Singh
Stock/Catalog Number: TAR4 (high Tg expressor) and TAR6 (low Tg expressor).
Primary:
Wils H, Kleinberger G, Janssens J, Pereson S, Joris G, Cuijt I, Smits V, Ceuterick-de
Groote C, Van Broeckhoven C, Kumar-Singh S. TDP-43 transgenic mice develop spastic
paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar
degeneration. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3858-63.
Abstract
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