Mouse Genome Informatics
tg1
    Tg(Prnp-TARDBP*A315T)95Balo/0
(129S1/SvImJ x B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: survival in F1 males is increased by 50-90 days as compared to males on the C57BL/6J background (J:203041)

digestive/alimentary system
• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background


Mouse Genome Informatics
tg2
    Tg(Prnp-TARDBP*A315T)95Balo/0
(ALR/LtJ x B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: survival in F1 males is increased by 50-90 days as compared to males on the C57BL/6J background (J:203041)

digestive/alimentary system
• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background


Mouse Genome Informatics
tg3
    Tg(Prnp-TARDBP*A315T)95Balo/0
(C3H/HeJ x B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: survival in F1 males is increased by more than 340 days as compared to males on the C57BL/6J background (J:203041)

digestive/alimentary system
• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background


Mouse Genome Informatics
tg4
    Tg(Prnp-TARDBP*A315T)95Balo/0
(FVB/NJ x B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: survival in F1 males is increased by 50-90 days as compared to males on the C57BL/6J background (J:203041)

digestive/alimentary system
• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background


Mouse Genome Informatics
tg5
    Tg(Prnp-TARDBP*A315T)95Balo/0
(PWK/PhJ x B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: survival in F1 males is increased by more than 340 days as compared to males on the C57BL/6J background (J:203041)

digestive/alimentary system
• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background


Mouse Genome Informatics
tg6
    Tg(Prnp-TARDBP*A315T)95Balo/0
(WSB/EiJ x B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: survival in F1 males is increased by more than 340 days as compared to males on the C57BL/6J background (J:203041)

digestive/alimentary system
• all F1 mice die with visible signs of gut pathology similar to mice on the C57BL/6J background


Mouse Genome Informatics
tg7
    Tg(Prnp-TARDBP*A315T)95Balo/0
B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• late onset difficulty in righting occurs suddenly and progresses rapidly especially in males
• mild deficit in the hindlimb reflex is observed in both male and female mice
• time-to-fall as measured by the hanging wire test is significantly decreased in transgenic males as compared to wild type littermates (J:203041)
• late onset immobility occurs suddenly and progresses rapidly especially in males
• both male and female mice exhibit a tendency to drag their tails when walking

digestive/alimentary system
• progressive decrease in number of fecal pellets excreted
• gut motility is significantly decreased beginning at day 60 in males and progresses to 282% of controls by day 90
• gut motility is significantly decreased in females but at later age than males and with less severity
• lower GI tract develops swelling, intra-intestinal coagulated blood, and necrotic tissue, however, pathology of upper digestive tract is normal

growth/size/body
• weight loss becomes significant at post-natal day 85 in males and post-natal day 127 in females
• late onset swollen and tender abdomen occurs suddenly and progresses rapidly especially in males

homeostasis/metabolism
• late onset dehydration occurs suddenly and progresses rapidly especially in males

integument
• late onset unkempt haircoat occurs suddenly and progresses rapidly especially in males

mortality/aging
• ovariectomy decreases female median survival by 94 days
• male castration decreases median survival by 10 days
• Background Sensitivity: death occurs at a median of 108 days in males
• Background Sensitivity: death occurs at a median of 185 days in females

nervous system
• ganglions in the superior mesentery appear smaller than control ganglions
• ganglions exhibit an increased percentage of condensed nuclei
• decreased AChE staining in the ganglion and intermodal strands of the myenteric plexus of the colon
• 80% decrease in the number of neurons per ganglion in the myenteric plexus of the colon, but not the duodenum, of 90-150 day old mice
• reactive astrocytosis observed in spinal cord lumbar sections from 80 day old males (J:203041)
• the large motor neurons of some males exhibit abnormally shaped nuclei (J:203041)
• small, but significant decrease in axon number and diameter in the sensory branch of the femoral nerve in 3 and 5 month old males (J:203041)
• some motor neurons have ubiquitin-positive cytoplasmic inclusions (J:203041)

skeleton
• late onset kyphosis occurs suddenly and progresses rapidly especially in males


Mouse Genome Informatics
tg8
    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/body
• 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