Phenotypes Associated with This Genotype

Genotype
MGI:4438492

• Allelic Composition: Tg(Thy1-TARDBP)4Singh/Tg(Thy1-TARDBP)4Singh
• Genetic Background: involves: C57BL/6J * SJL/J

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

mortality/aging

premature death ( J:157550 )

• average survival time is 24 days

behavior/neurological

limb grasping ( J:157550 )

• at about 14 days of age mice develop hindlimb grasping

impaired coordination ( J:157550 )

• show a statistically significant about 2.5 fold reduced performance on rotarod

abnormal limb posture ( J:157550 )

• wide based stance

abnormal gait ( J:157550 )

• wide based stance, small stride, and frequent off line stumbling

short stride length ( J:157550 )

• footprint analysis shows a significant about 2 fold decrease in the stride of hindlimbs and of forelimbs

paralysis ( J:157550 )

• after about 22 days of age, an extremely rapid disease progression begins with mice becoming completely paralyzed and dying within 3-4 days

muscle

facial muscle spasm ( J:157550 )

• at about 22 days of age, spasms of facial muscles are observed

facial muscle fasciculation ( J:157550 )

• at about 22 days of age, fasciculations of facial muscles are observed

nervous system

microgliosis ( J:157550 )

• highly transgene dose dependent

abnormal hippocampus morphology ( J:157550 )

• large neuronal cytoplasmic and intranuclear inclusions are present to some extent in hippocampal/subicular neurons

• neuronal loss is seen in all affected brain regions

abnormal hippocampus CA3 region morphology ( J:157550 )

• loss of CA3 hippocampal neurons and degeneration of Purkinje cells

abnormal subiculum morphology ( J:157550 )

• large neuronal cytoplasmic and intranuclear inclusions are present to some extent in hippocampal/subicular neurons

• neuronal loss is seen in all affected brain regions

abnormal neocortex morphology ( J:157550 )

• large neuronal cytoplasmic and intranuclear inclusions are present in cortical layer V of the anterior cortex including the primary motor cortex

• neuronal loss is seen in all affected brain regions including both the superficial and deep cortical layers of the anterior cortex

abnormal somatosensory cortex morphology ( J:157550 )

• large neuronal cytoplasmic and intranuclear inclusions are present in somatosensory areas of the hind- and forelimbs

• neuronal loss is seen in all affected brain regions

Purkinje cell degeneration ( J:157550 )

astrocytosis ( J:157550 )

• highly transgene dose dependent

decreased neuron number ( J:157550 )

• neuronal loss is seen in all affected brain regions including both the superficial and deep cortical layers of the anterior cortex

• large neuronal cytoplasmic and intranuclear inclusions are present in somatosensory areas of the hind- and forelimbs

neuronal intranuclear inclusions ( J:157550 )

• present in cortical layer V of the anterior cortex including the primary motor cortex and somatosensory areas of the hind- and forelimbs and to some extent in the hippocampal/subicular neurons

abnormal spinal cord morphology ( J:157550 )

• number of neurons in the lumbosacral region is significantly lower

decreased motor neuron number ( J:157550 )

• quantitative neuronal loss is shown in motor cortex at 24 days

• number of neurons in the lumbosacral region of the spinal cord is significantly lower

motor neuron degeneration ( J:157550 )

• vacuolar degeneration of several cranial motor nuclei is observed

abnormal spinal cord ventral horn morphology ( J:157550 )

• atrophy and increased number of pyknotic neurons in the ventral horn region of the lumbosacral and cervical spinal cord occurs in a transgene dose dependent manner

hematopoietic system

microgliosis ( J:157550 )

• highly transgene dose dependent

immune system

microgliosis ( J:157550 )

• highly transgene dose dependent

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 10		DOID:0060201	OMIM:612069	J:157550
frontotemporal dementia		DOID:9255	OMIM:600274	J:157550