Posted 7 December 2010

General Information

Total RNA was extracted from human brain with RNeasy Plus Mini Kit and reverse transcribed into hTDP-43. The cDNA containing ~35 bp of the 5’UTR and 24 bp of the 3’UTR was inserted into the XhoI site of the MoPrP vector. The linearized transgene was microinjected into fertilized C57BL/6 (B6) mouse eggs. Six founders were mated to B6 mice.

Mutation: Full length hTDP-43.

Promoter: Mouse prion promoter.

Mouse strain: C57BL/6; Background: C57BL/6.

Phenotype

Neuropathological analysis:

Expression of hTDP-43 caused a dose-dependent down regulation of mouse TDP-43 RNA and protein. Moderate over-expression of hTDP-43 resulted in TDP-43 truncation, increased cytoplasmic and nuclear ubiquitin levels, and intranuclear and cytoplasmic aggregates that were immunopositive for phosphorylated TDP-43.

Behavioral Phenotype:

Mice showed reactive gliosis, axonal and myelin degeneration, gait abnormalities, and early lethality.

Availability

Contact: (Licensing/academic distribution contact information)
Dr. Jada Lewis
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224

References

Primary:

Xu YF, Gendron TF, Zhang YJ, Lin WL, D'Alton S, Sheng H, Casey MC, Tong J, Knight J, Yu X, Rademakers R, Boylan K, Hutton M, McGowan E, Dickson DW, Lewis J, Petrucelli L. Wild-Type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J Neurosci. 2010 Aug 11;30(32):10851-9. Abstract