Posted 7 December 2010
1,245-bp full-length mouse TDP-43 cDNA was cloned into the EcoRV site of pNN265,
a modified form of pcDNAI/Amp. A 2.7-kb NotI fragment was isolated from pNN265 and
cloned into the NotI site of the vector pMM403 containing 8.5 kb of the mouse CaMKII
promoter region resulting in pCaMKII-TDP-43. An 11.2-kb SfiI fragment was then purified
from pCaMKII-TDP-43 and injected into the one-cell embryos of FVB/N mice. 10 offsprings
were identified as the founders. The FVB/N founders were bred with WT FVB/N mice,
and three of them were germline transmitted. Each of the three germlines transmitted,
CamKII-TDP-43 Tg lines were set to littermate intercrosses within the line so to
obtain three homozygous TDP-43 Tg mouse lines.
Promoter: Ca2+/calmodulin-dependent kinase II (CaMKII) promoter.
Mouse strain: FVB/N background; F8.
Three tg lines generated with ~2x TDP-43 expression than WT in cortex and hippocampus.
TDP-43 OE in hippocampus, cortex, and striatum. This OE leads to the formation of
TDP-43+, ubiquitin+ NCIs and neurodegeneration.
Mice exhibit learning and memory deficits, progressive motor dysfunction and hippocampal
Contact: Che-Kun James Shen
Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan
Wu LS, Cheng WC, Hou SC, Yan YT, Jiang ST, Shen CK. TDP-43, a neuro-pathosignature
factor, is essential for early mouse embryogenesis. Genesis. 2010 Jan;48(1):56-62.
Tsai KJ, Yang CH, Fang YH, Cho KH, Chien WL, Wang WT, Wu TW, Lin CP, Fu WM, Shen
CK. Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause
neurological and pathological phenotypes mimicking FTLD-U. J Exp Med. 2010 Aug 2;207(8):1661-73.