Mouse Genome Informatics
tg1
    Tg(Prnp-TARDBP)3cPtrc/Tg(Prnp-TARDBP)3cPtrc
C57BL/6-Tg(Prnp-TARDBP)3cPtrc
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants become moribound between 1 and 2 months of age

growth/size
• body weight is reduced from 14 days of age onward

behavior/neurological
• between 1 and 2 months of age, mutants are unable to right themselves
• mutants fail to show proper escape extension by splaying their hindlimbs upon elevation
• mutants exhibit body tremors by 21 days of age
• however, there is no evidence of muscle atrophy
• mutants develop an aberrant "swimming" gait
• by 21 days of age, mutants have difficulty walking faster than 10 cm/s and recruiting their hindlimbs

nervous system
• brain weight is lower at 1 month of age
• in the brainstem, eosinphilic aggregates are found mostly within the pontine nuclei and midbrain tegmentum, including the red nucleus
• eosinphilic aggregates
• reactive gliosis is seen in the anterior horn of the spinal cord
• reactive astrocytosis is seen in the gray matter of the spinal cord
• mutants exhibit neuronal cytoplasmic eosinophilic aggregates in spinal motor neurons
• about 10% of neurons in the anterior horn of the spinal cord had eosinophilic aggregates, with fewer in the posterior horn and brainstem
• motoneuron eosinophilic aggregates are composed of abnormal mitochondrial clusters; mitochondria have features suggestive of degeneration, with decreased cristae and vacuoles within the mitochondrial matrix
• degenerating neurites, axons and neurons are seen in the spinal cord
• degenerating mitochondria, and autophagic vacuoles, are seen within swollen axons in the spinal cord white matter
• in the spinal cord
• vacuolization of myelin and myelin ovoids indicate myelin degeneration in anterolateral funiculi of the spinal cord