Animal models

All experiments were in accordance with the guidelines of the Institute of Animal Use and Care Committee at National Cheng Kung University (NCKU), Taiwan. Mice were bred at the NCKU laboratory animal center. Water and food were provided ad libitum. The FTLD-TDP transgenic mouse model expressed the full-length mouse TDP-43 cDNA under the control of an 8.5-kb calcium/calmodulin-dependent protein kinase II (CaMKII) promoter and overexpressed TDP-43 in the forebrain. PCR genotyping was performed to identify whether the mice were transgene-positive. Six months old FTLD-TDP transgenic mice showed cytosolic TDP-43 aggregation accompanied by nuclear TDP-43 depletion in the brain, which mimics the hallmarks of TDP-43 proteinopathy in the brains of FTLD-TDP patients ²⁶.