Phenotypes Associated with This Genotype

Genotype
MGI:6404636

• Allelic Composition: Tardbp^tm3.1Ckjs/Tardbp⁺
• Genetic Background: involves: C57BL/6J

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

mortality/aging

premature death ( J:285792 )

• males show a shorter life span, with an average of 19.5 +/- 2 months

• survival of females is longer than males, with average age being 25.5 +/- 6 months

• male-to-female ratio of the surviving pups is 1 to 2.6

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:285792 )

• males exhibit motor dysfunction at 6 months of age or older

• however, young and old males do not show impaired performance on the T-maze task

• disease onset in females is highly variable and about 30% of females are indistinguishable from wild-type females

limb grasping ( J:285792 )

♂ • males start to show hind limb-clasping around 8 months of age

tremors ( J:285792 )

♂ • mice exhibit spastic and trembled gait at 18 months and beyond

impaired coordination ( J:285792 )

♂ • males show a shorter latency to fall than wild-type mice starting after 5 months of age

hindlimb paralysis ( J:285792 )

♂ • males develop hindlimb paralysis with age

spasticity ( J:285792 )

♂ • mice exhibit spastic and trembled gait at 18 months and beyond

growth/size/body

weight loss ( J:285792 )

♂ • males lose weight after 18 months of age

muscle

skeletal muscle atrophy ( J:285792 )

♂ • 12 and 24 month old males exhibit skeletal muscle atrophy, with a decrease in wet weight of soleus muscle and reduction of calf muscle volume

nervous system

astrocytosis ( J:285792 )

♂ • astrogliosis is seen in the spinal cord in aged, but not 6 month, mice

abnormal motor neuron morphology ( J:285792 )

♂ • the level of ubiquitinated proteins is increased in the ChAT+ motor neurons of spinal cord of 6 month or older males, most of which are in the cytosol

motor neuron degeneration ( J:285792 )

♂ • males show an age-dependent loss of spinal cord motor neurons, with nearly 30%, 62%, and 77% loss at 6 months, 12 months, and 24 months, respectively

♂ • 30% loss of motor neurons in the lumbar region of the spinal cord at 6 months of age while the motor cortex, especially the primary motor cortex, only shows NeuN+ neuron loss at 24 months of age, indicating that lower motor neurons are affected first and then pathology spreads to the upper motor neurons

♂ • however, males do not show loss of neurons in the dentate gyrus, CA1 or CA3 regions of hippocampus

abnormal neuromuscular synapse morphology ( J:285792 )

♂ • 6 month old males show denervation of the neuromuscular junction of soleus muscle which progresses with ageing

neuronal cytoplasmic inclusions ( J:285792 )

♂ • TDP-43+ aggregates appear in the cytosol of spinal cord motor neurons of 12 and 24 month old males and colocalize with ubiquitinated proteins

skeleton

kyphosis ( J:285792 )

♂ • males start to show kyphosis at around 8 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:285792