Mouse Genome Informatics
cx
    Tg(Camk2a-tTA)1Mmay/0
Tg(tetO-MAPT*P301L)#Kha/0

involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
behavior/neurological
• reduction in exploration in open-field tests
• mutants first exhibit impaired spatial reference memory at 2.5 months of age, showing a slightly reduced search bias for the target quadrant than controls in the Morris water maze
• spatial memory retention becomes more impaired with age, especially after 4 months of age, with the mean probe performance being equal to random swimming, indicating little or no retention of spatial memory
• mutants exhibit cognitive impairments in the acquisition phases of the Morris water maze, showing a longer mean distance to locate the hidden platform
• clasping and limb retraction when lifted by the tail
• mutants exhibit longer latencies to traverse a beam
• mutants develop an age-dependent increase in the time taken to start swimming, however they are able to achieve comparable mean swim speeds during probe trials
• from about 9.5 months of age, the most severely affected mutants develop hunched posture with hindlimb dysfunction and tail rigor
• develop dystonic posture with tail rigor at 9.5 months of age
• from about 9.5 months of age, the most severely affected mutants exhibit decreased ambulation

growth/size/body
• from about 9.5 months of age, the most severely affected mutants exhibit decreased body weight

nervous system
• 4-7% reduction in brain weight at 4 months of age
• atrophy of the forebrain is seen by 5 months of age
• age-dependent progression of tau processing that results in pathophysiological deposition of tau as mature tangles in the brain
• mutants exhibit age-dependent progression of neurofibrillary tangle formation, with tangles first appearing in the neocortex and then progressing into the hippocampus and limbic structures with increasing age
• neurofibrillary tangles develop in the hippocampus in a distinct pattern; mature tangles occur initially in CA1 pyramidal neurons, spread to CA2, and by 8.5 months of age include pyramidal neurons in CA2 and granular neurons of the dentate gyrus
• abnormal conformations of tau are present in the hippocampus and neocortex of 2.5-month old mutants
• reactive astrocytes in forebrains of 10 month old mutants
• atrophy of the dorsal corticospinal tracts accompanied by loss of neurofilament
• degeneration in the hippocampus and neocortex is seen in 10 month old mutants
• massive neuronal loss, most apparent in the CA1 region of the hippocampus
• spinal cords appear thinner, however, no decrease in motor neuron density is seen

muscle
• develop dystonic posture with tail rigor at 9.5 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:102973
Frontotemporal Dementia; FTD 600274 J:102973