Mouse Genome Informatics
tg
    Tg(TARDBP*G348C)#Jpj/0
involves: C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
behavior/neurological
• in the passive avoidance test, mutants exhibit severe cognitive impairments after 7 months of age and especially in the 11th and 13th months
• mice exhibit a learning impairment in the Barnes maze test at 10 months of age, showing a reduction in the time spent in the target quadrant and increased primary errors
• in the probe trial, mutants show a reduction in the time spent in the target quadrant and an increase in the total number of errors
• mice show reduction in latency in the accelerating rotarod tests starting at around 42 weeks of age, indicating age-related motor deficits

nervous system
• age dependent microgliosis and astrogliosis in the brain and spinal cord; mircrogliosis and astrogliosis is more pronounced than in mice expressing the wild-type or the A315T transgene
• age dependent microgliosis and astrogliosis in the brain and spinal cord; mircrogliosis and astrogliosis is more pronounced than in mice expressing the wild-type or the A315T transgene
• 10% increase (an increase of 100 axons) in the number of motor axons with 1-3 um caliber and a 12% decrease (a decrease of 120 axons) in the number of motor axons with 6-9 um caliber in 10 month old mutants
• 10% of analyzed neuromuscular junctions are denervated in 10 month old mutants, while over 20% are partially denervated
• many caspase-3 positive neurons are seen in the spinal cord at 10 months of age, indicating neuronal damage
• mice develop ubiquitinated and TARDBP+ inclusions in the spinal cord by 10 months of age
• abnormal accumulation of neurofilament and peripherin proteins in inclusions in large motor neurons and the brain at 10 months of age, indicating degeneration of motor neurons

immune system
• age dependent microgliosis and astrogliosis in the brain and spinal cord; mircrogliosis and astrogliosis is more pronounced than in mice expressing the wild-type or the A315T transgene
• levels of various cytokine and chemokine mRNAs are upregulated indicating neuroinflammation

hematopoietic system
• age dependent microgliosis and astrogliosis in the brain and spinal cord; mircrogliosis and astrogliosis is more pronounced than in mice expressing the wild-type or the A315T transgene

homeostasis/metabolism
• levels of various cytokine and chemokine mRNAs are upregulated indicating neuroinflammation

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:195184
Frontotemporal Lobar Degeneration with Tdp43 Inclusions, Grn-Related 607485 J:195184