Phenotypes Associated with This Genotype

Genotype
MGI:5448853

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-TARDBP*)4Vle/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

abnormal dentate gyrus morphology ( J:170756 )

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

gliosis ( J:170756 )

• 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

abnormal corticospinal tract morphology ( J:170756 )

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

• however, lower motor neuron loss is not observed

abnormal neuron morphology ( J:170756 )

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

neurodegeneration ( J:170756 )

• 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

limb grasping ( J:170756 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:170756