Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fgf14Tg(tetO-MAPT*P301L)4510Kha mutation
(2 available);
any
Fgf14 mutation
(40 available)
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
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nervous system
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• a significant loss in brain weight by 5.5 months
• when treated with doxycycline during 5.5 to 10 months, the loss of brain weight was significantly protected
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• significant decrease in total numbers of CA1 hippocampal neurons
• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment
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• gross atrophy of the forebrain was evident in a 10-month-old mouse
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• develop argyrophilic tangle-like inclusions in the cortex by 4 months and in the hippocampal formation by 5.5 months
• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress
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• the neuronal inclusions composed of a mass of straight tau filaments
• when treated with doxycycline at 2.5 month, the tau pathology ceased to progress
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• approximately 23% of CA1 pyramidal cells remaining at 8.5 months
• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment
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behavior/neurological
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• he retention of spatial memory examined by the Morris water maze were impaired as the mice aged
• deficit in spatial navigation was also seen in younger mice
• the performance improved when treated with doxycycline at 2.5 month-old or at 5.5 month-old
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fgf14Tg(tetO-MAPT*P301L)4510Kha mutation
(2 available);
any
Fgf14 mutation
(40 available)
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
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behavior/neurological
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• progressive decrease in percent of time spent freezing in response to unconditioned stimulus beginning at 2 months of age
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• progressive decrease in percent of time spent freezing in response to conditioned stimulus beginning at 6 months of age
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• amount of time spent in open arms of elevated plus maze is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months
• higher ratio of time spent in open not closed arms relative to nontransgenic mice at 10 months of age, but not 2 or 6 months
• exploration of light chamber is increased relative to nontransgenic mice at 6 months of age, but not 2 or 10 months
• higher ratio of time spent in light not dark relative to nontransgenic miceat 10 months of age, but not 2 or 6 months
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• decreased tendency to explore the center of the open field relative to nontransgenic mice
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• mice exhibit progressive hyperactivity in open field analysis and elevated plus maze
• total distance travelled in open field assay is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months
• average speed is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months
• total time spent mobile is increased relative to nontransgenic mice at 6 and 10 months of age, but not 2 months
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nervous system
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• neurofibrilliary tangles are observed by immunostaining in the CA1 region of the hippocampus beginning at 6 months of age and progressing to an extensive pathology by 11 months of age
• neurofibrilliary tangles are observed by immunostaining in the amygdala beginning at 2 months of age and progressing to an extensive pathology by 10 months of age
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• tau burden increases with age in the amygdala and CA1 region of the hippocampus
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fgf14Tg(tetO-MAPT*P301L)4510Kha mutation
(2 available);
any
Fgf14 mutation
(40 available)
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
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nervous system
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• progressive atrophy of dentate granule cells
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• progressive atrophy of hippocampal pyramidal neurons
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fgf14Tg(tetO-MAPT*P301L)4510Kha mutation
(2 available);
any
Fgf14 mutation
(40 available)
Tg(Camk2a-tTA)1Mmay mutation
(8 available)
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behavior/neurological
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• reduction in exploration in open-field tests
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• 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
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• clasping and limb retraction when lifted by the tail
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• develop dystonic posture with tail rigor at 9.5 months of age
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• mutants exhibit longer latencies to traverse a beam
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• 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
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• from about 9.5 months of age, the most severely affected mutants develop hunched posture with hindlimb dysfunction and tail rigor
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• from about 9.5 months of age, the most severely affected mutants exhibit decreased ambulation
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growth/size/body
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• from about 9.5 months of age, the most severely affected mutants exhibit decreased body weight
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nervous system
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• 4-7% reduction in brain weight at 4 months of age
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• atrophy of the forebrain is seen by 5 months of age
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• 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
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• abnormal conformations of tau are present in the hippocampus and neocortex of 2.5-month old mutants
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• reactive astrocytes in forebrains of 10 month old mutants
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• atrophy of the dorsal corticospinal tracts accompanied by loss of neurofilament
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• degeneration in the hippocampus and neocortex is seen in 10 month old mutants
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• massive neuronal loss, most apparent in the CA1 region of the hippocampus
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• spinal cords appear thinner, however, no decrease in motor neuron density is seen
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muscle
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• develop dystonic posture with tail rigor at 9.5 months of age
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