Mouse Genome Informatics
tg1
    Tg(Thy1-TARDBP)4Singh/Tg(Thy1-TARDBP)4Singh
involves: C57BL/6J * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• average survival time is 24 days

behavior/neurological
• at about 14 days of age mice develop hindlimb grasping
• show a statistically significant about 2.5 fold reduced performance on rotarod
• wide based stance
• wide based stance, small stride, and frequent off line stumbling
• footprint analysis shows a significant about 2 fold decrease in the stride of hindlimbs and of forelimbs
• after about 22 days of age, an extremely rapid disease progression begins with mice becoming completely paralyzed and dying within 3-4 days

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

nervous system
• highly transgene dose dependent
• large neuronal cytoplasmic and intranuclear inclusions are present to some extent in hippocampal/subicular neurons
• neuronal loss is seen in all affected brain regions
• loss of CA3 hippocampal neurons and degeneration of Purkinje cells
• large neuronal cytoplasmic and intranuclear inclusions are present to some extent in hippocampal/subicular neurons
• neuronal loss is seen in all affected brain regions
• 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
• 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
• highly transgene dose dependent
• 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
• 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
• number of neurons in the lumbosacral region is significantly lower
• 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
• vacuolar degeneration of several cranial motor nuclei is observed
• 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
• highly transgene dose dependent

immune system
• highly transgene dose dependent


Mouse Genome Informatics
tg2
    Tg(Thy1-TARDBP)4Singh/0
involves: C57BL/6J * SJL/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• abnormal limb reflex at about 14 months of age
• 40% reduced motor performance at about 15 months of age

nervous system
• highly transgene dose dependent
• large neuronal cytoplasmic and intranuclear inclusions are present to some extent in hippocampal/subicular neurons
• large neuronal cytoplasmic and intranuclear inclusions are present to some extent in hippocampal/subicular neurons
• large neuronal cytoplasmic and intranuclear inclusions are present in cortical layer V of the anterior cortex including the primary motor cortex
• large neuronal cytoplasmic and intranuclear inclusions are present in somatosensory areas of the hind- and forelimbs
• highly transgene dose dependent
• 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
• 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
• highly transgene dose dependent

immune system
• highly transgene dose dependent