Phenotypes Associated with This Genotype

Genotype
MGI:4438493

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

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

mortality/aging

premature death ( J:157550 )

• average survival of 6.7 months

behavior/neurological

limb grasping ( J:157550 )

• develops abnormal limb reflex at 2 months

impaired coordination ( J:157550 )

• shows up to 6 fold reduced motor performance at about 4 months of age

nervous system

increased neuron apoptosis ( J:157550 )

• increase level of activated caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP)

• decreased number of neurons in the lumbosacral region.

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 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

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 6 months

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

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

cellular

increased neuron apoptosis ( J:157550 )

• increase level of activated caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP)

• decreased number of neurons in the lumbosacral region.

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