Phenotypes associated with this allele

• Allele Symbol: Tg(Prnp-TARDBP*Q331K)31Dwc
• Allele Name: transgene insertion 31, Don W Cleveland
• Allele ID: MGI:5825215
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Prnp-TARDBP)96Dwc/0 Tg(Prnp-TARDBP*Q331K)31Dwc/0	involves: C3H * C57BL/6	MGI:5828862
tg2	Tg(Prnp-TARDBP*Q331K)31Dwc/?	involves: C3H * C57BL/6	MGI:5828845

Genotype
MGI:5828862

cx1

• 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 )

• mice lack the ability to raise pelvis from ground

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

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

Genotype
MGI:5828845

tg2

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

behavior/neurological

limb grasping ( J:239141 )

tremors ( J:239141 )

• mild tremors

impaired coordination ( J:239141 )

• mild, progressive motor dysfunction as assessed by rotarod

hematopoietic system

microgliosis ( J:239141 )

• modest increase in microglial activation in white matter tracts of the spinal cord as compared to controls

• microgliosis is observed in layer V of the cortex of 24 month old mice

immune system

microgliosis ( J:239141 )

• modest increase in microglial activation in white matter tracts of the spinal cord as compared to controls

• microgliosis is observed in layer V of the cortex of 24 month old mice

muscle

abnormal skeletal muscle fiber morphology ( J:239141 )

• mild disorganization of muscle fibers in aged mice

nervous system

microgliosis ( J:239141 )

• modest increase in microglial activation in white matter tracts of the spinal cord as compared to controls

• microgliosis is observed in layer V of the cortex of 24 month old mice

decreased cerebral cortex pyramidal cell number ( J:239141 )

• loss (14%) of pyramidal neurons from the cortex in 24 month old mice

abnormal neocortex morphology ( J:239141 )

• microgliosis is observed in layer V of the cortex of 24 month old mice

• mild astrogliosis is observed in layer V of the cortex of young mice

astrocytosis ( J:239141 )

• astrogliosis is detected in the anterior horn of the spinal cord

• mild astrogliosis is observed in layer V of the cortex of young mice

abnormal neuromuscular synapse morphology ( J:239141 )

• mild (15%) reduction in intact neuromuscular junctions (NMJ) is observed in young mice

• 35% reduction in number of intact neuromuscular junctions in aged mice

• reduction in NMJ area is observed in 24 month old mice

neuronal cytoplasmic inclusions ( J:239141 )

• small, but increasing number of cytoplasmic p62+ inclusions are observed in spinal cord of 8 week old mice; ubiquitin aggregation is not observed

• small cytoplasmic p62+ and TARDBP inclusions, as well as occasional ubiquitin inclusions are observed in motor and somatosensory cortices of 24 month old mice

neuronal intranuclear inclusions ( J:239141 )

• occasional TARDBP inclusions are observed in neuropil of 24 month old mice

• small number of ubiquitin and p62 + aggregates observed in motor cortex of 8 week and 24 month animals

abnormal spinal cord ventral horn morphology ( J:239141 )

• astrogliosis is detected in the anterior horn of the spinal cord

• modest increase microglial activation in white matter tracts of the spinal cord

• small, but increasing number of cytoplasmic p62+ inclusions are observed in spinal cord of 8 week old mice; ubiquitin aggregation is not observed