Mouse Genome Informatics
tg
    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

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 10, with or without Frontotemporal Dementia; 612069 J:163231
Frontotemporal Lobar Degeneration with Tdp43 Inclusions, Grn-Related 607485 J:163231