Phenotypes Associated with This Genotype

Genotype
MGI:5828862

• Allelic Composition: Tg(Prnp-TARDBP)96Dwc/0; Tg(Prnp-TARDBP*Q331K)31Dwc/0
• Genetic Background: involves: C3H * C57BL/6

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

hematopoietic system

microgliosis ( J:239141 )

• mild gliosis is observed in anterior horn of spinal cord in young mice

• moderate gliosis is observed in white matter tracts

• mild increase in CD68+ microgliosis in layer V

nervous system

microgliosis ( J:239141 )

• mild gliosis is observed in anterior horn of spinal cord in young mice

• moderate gliosis is observed in white matter tracts

• mild increase in CD68+ microgliosis in layer V

abnormal neocortex morphology ( J:239141 )

• loss of alpha motor neurons in layer V region of the cortex

• 46% loss of large caliber alpha-motor axons in L5 nerve root at 8 weeks of age

• decreased numbers of pyramidal neurons in layer V

• astrogliosis is observed in layer V of cortex of young animals

• mild increase in CD68+ microgliosis in layer V

abnormal primary motor cortex morphology ( J:239141 )

• small cytoplasmic p62+ and TARDBP inclusions, as well as occasional ubiquitin inclusions are observed in motor and somatosensory cortices of 8 week old mice

abnormal somatosensory cortex morphology ( J:239141 )

• small cytoplasmic p62+ and TARDBP inclusions, as well as occasional ubiquitin inclusions are observed in motor and somatosensory cortices of 8 week old mice

astrocytosis ( J:239141 )

• astrogliosis is observed in layer V of cortex of young animals

• astrogliosis is observed in anterior horn of spinal cord in young mice

abnormal axon morphology ( J:239141 )

• 46% loss of large caliber alpha-motor axons in L5 nerve root at 8 weeks of age

• axon degeneration is characterized by vacuolization and myelin defects

decreased neuron number ( J:239141 )

• 70% loss of alpha motor neurons in anterior horn of lumbar spinal cord

• loss of alpha motor neurons in layer V region of the cortex

• decreased numbers of pyramidal neurons in layer V

decreased cerebral cortex pyramidal cell number ( J:239141 )

• decreased numbers of pyramidal neurons in layer V

abnormal neuromuscular synapse morphology ( J:239141 )

• 60% reduction in intact neuromuscular junctions in 8 week old mice

• reduction in NMJ area in 8 week old mice

neuronal cytoplasmic inclusions ( J:239141 )

• frequent globular cytoplasmic inclusions are observed in spinal cord at 8 weeks of age

• a small number of ubiquitin and p62+ inclusions are observed in spinal cord of 8 week old mice

• small cytoplasmic p62+ and TARDBP inclusions, as well as occasional ubiquitin inclusions are observed in motor and somatosensory cortices of 8 week old mice

neuronal intranuclear inclusions ( J:239141 )

• multiple small globular inclusions in neuropil of ventral horns

• nuclear aggregation of endogenous TDP-43 in 8 week old mice

abnormal spinal cord ventral horn morphology ( J:239141 )

• astrogliosis and mild gliosis in anterior horn of spinal cord in young mice

• frequent globular cytoplasmic inclusions are observed in spinal cord at 8 weeks of age

• multiple small globular inclusions in neuropil of ventral horns

• moderate gliosis is observed in white matter tracts

decreased spinal cord ventral horn cell number ( J:239141 )

• 70% loss of alpha motor neurons in anterior horn of lumbar spinal cord

neurodegeneration ( J:239141 )

neuron degeneration ( J:239141 )

• progressive motor and cortical neuron degeneration

immune system

microgliosis ( J:239141 )

• mild gliosis is observed in anterior horn of spinal cord in young mice

• moderate gliosis is observed in white matter tracts

• mild increase in CD68+ microgliosis in layer V

mortality/aging

premature death ( J:239141 )

• average survival time is 64 +/- 4 days

muscle

skeletal muscle fiber degeneration ( J:239141 )

• muscle fiber atrophy

behavior/neurological

limb grasping ( J:239141 )

• failure to splay limbs normally when lifted by tail

tremors ( J:239141 )

• tremor observed beginning at 3 weeks of age

impaired coordination ( J:239141 )

• rapid decline in motor function from 3 weeks of age

• decline in performance on rotarod beginning at 5 weeks of age as compared to controls

abnormal gait ( J:239141 )

• severely stilted gait

hindlimb paralysis ( J:239141 )

• progressive, severe hind-limb paralysis beginning at 5-6 weeks of age

• mice lack the ability to raise pelvis from ground

digestive/alimentary system

digestive/alimentary phenotype ( J:239141 )

N • no intestinal blockage or megacolon is observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:239141