• about 50% loss of dentate gyrus neurons at 1 month after Dox removal

• massive gliosis in cortical and hippocampal regions following Dox removal

• gliosis in the corticospinal tract, including the striatum, cerebral peduncles, medullary pyramids, and cervical spinal cord, following Dox removal

• selective loss of corticospinal tract axons in cervical spinal cord associated with glisosis following Dox removal

• however, lower motor neuron loss is not observed

• mutants rarely show accumulation of hyperphosphorylated, ubiquitinated cytoplasmic aggregates of TARDBP in neurons following Dox removal (around 1% of neurons showing aggregates)

• mutants switched to a doxycycline (dox)-free diet at 28 days of age show progressive neurodegeneration; neuron loss is particularly evident in the deep neocortical layers and in the dentate gyrus but is rarely seen in the hippocampal CA1 subfield and the olfactory bulb

• selective loss of corticospinal tract axons in cervical spinal cord following Dox removal

• abnormal limb clasping as early as 1 week after dox removal that continues throughout life until sacrifice