Mouse Genome Informatics
tg
    Tg(Prnp-TARDBP*A315T)95Balo/0
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• average survival is 154 days; at end-stage, mice die spontaneously or are euthanized when they lose righting reflex or can no longer obtain food and water

growth/size
• mice begin losing weight around 4.5 months of age

behavior/neurological
• at 3-4 months mice develop abnormal gait; around 4.5 months, mice exhibit a "swimming" gait when they lose ability to support their body weight but still use their limbs for propulsion to slide on their stomachs

nervous system
• activation of astrocytes is detected in layer 5 with reactive astrocytosis seen around degenerating neurons
• late-stage mice have cytoplasmic accumulation of ubiquinated proteins in neurons of cortical layer 5; these neurons are prominent in the motor cortex and are also present in orbital, cingulated, sensory and other cortical regions
• no ubiquinated protein aggregates are observed in the caudate/putamen, substantia nigra, thalamus or other structures at any stage
• neuron loss in cortical layer 5
• fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns
• femoral motor and sensory nerves shows loss of axons with ongoing axonal degeneration in the motor branch
• fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns
• in end-stage mice, about a 20% loss of spinal motor neurons is observed
• presence of ubiquitinated protein accumulations is detected preferentially in large neurons of the dorsal horn as well as scattered interneurons

muscle
• end-stage mice have scattered and grouped atrophic muscle fibers, characteristic of muscle denervation
• atrophic muscle fibers are observed in end-stage mice
• electromyography in end-stage mice shows numerous fibrillation potentials indicative of loss of muscle fiber innervation and fasciculations, which are spontaneous firing of motor units often seen with human motor neuron diseases; in presymptomatic and early-stage mice, electromyography is normal
• around 4.5 months, mice can no longer support their body weight

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 10, with or without Frontotemporal Dementia; 612069 J:153197
Frontotemporal Dementia; FTD 600274 J:153197