Mouse Genome Informatics
cx
    Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-TARDBP*)4Vle/0

involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
nervous system
• 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 gliosis 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

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

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 10, with or without Frontotemporal Dementia; 612069 J:170756