These transgenic mice express the mutant human TARDBP, TAR DNA binding protein, hTDP-43-deltaNLS, with a defective nuclear localization signal, under the direction of the tetO, tetracycline operator promoter. Mice hemizygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. It is not known if homozygotes are viable. When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of the hTDP-43-deltaNLS protein may be regulated with tetracycline or its analog doxycycline (DOX) in the double mutant offspring.
When mated to Camk2a-tTA mice which express tTA in forebrain neurons (See for example: Stock No. 003010; Stock No. 007004; Stock No. 010712), the resulting bitransgenic mice exhibit progressive neurodegeneration in the cortex and hippocampus, corticospinal tract degeneration, gliosis and spastic motor impairment. One month after DOX removal, bitransgenic mice have lost approximately 50% of hippocampal dentate gyrus neurons.
