Phenotypes associated with this allele

• Allele Symbol: Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}
• Allele Name: transgene insertion 4510, Karen Hsiao Ashe
• Allele ID: MGI:4819866
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Camk2a-tTA)1Mmay/? Fgf14^Tg(tetO-MAPT*P301L)4510Kha/?	involves: 129S6/SvEvTac * FVB/N	MGI:4819951
cx2	Tg(Camk2a-tTA)1Mmay/0 Fgf14^Tg(tetO-MAPT*P301L)4510Kha/Fgf14^+	involves: 129S6/SvEvTac * FVB/N	MGI:5558945
cx3	Tg(Camk2a-tTA)1Mmay/0 Fgf14^Tg(tetO-MAPT*P301L)4510Kha/Fgf14^+	involves: 129/Sv * C57BL/6 * CBA * FVB/N	MGI:5438795
cx4	Tg(Camk2a-tTA)1Mmay/0 Fgf14^Tg(tetO-MAPT*P301L)4510Kha/Fgf14^+	involves: FVB/N	MGI:5511058

Genotype
MGI:4819951

cx1

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/?; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/?
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

decreased brain weight ( J:99626 )

• 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

abnormal hippocampus CA1 region morphology ( J:99626 )

• significant decrease in total numbers of CA1 hippocampal neurons

• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment

forebrain atrophy ( J:99626 )

• gross atrophy of the forebrain was evident in a 10-month-old mouse

neurofibrillary tangles ( J:99626 )

• 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

abnormal neuron morphology ( J:99626 )

• 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

decreased hippocampus pyramidal cell number ( J:99626 )

• approximately 23% of CA1 pyramidal cells remaining at 8.5 months

• CA1 neuron estimates were stabilized after brief (6- to 8-week) doxycycline treatment

behavior/neurological

abnormal spatial learning ( J:99626 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:99626

Genotype
MGI:5558945

cx2

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/Fgf14⁺
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

behavior/neurological

impaired contextual conditioning behavior ( J:207366 )

• progressive decrease in percent of time spent freezing in response to unconditioned stimulus beginning at 2 months of age

impaired cued conditioning behavior ( J:207366 )

• progressive decrease in percent of time spent freezing in response to conditioned stimulus beginning at 6 months of age

increased exploration in new environment ( J:207366 )

abnormal anxiety-related response ( J:207366 )

decreased anxiety-related response ( J:207366 )

• 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

increased anxiety-related response ( J:207366 )

• decreased tendency to explore the center of the open field relative to nontransgenic mice

increased locomotor activity ( J:207366 )

• 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

nervous system

neurofibrillary tangles ( J:207366 )

• 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

tau protein deposits ( J:207366 )

• tau burden increases with age in the amygdala and CA1 region of the hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:207366

Genotype
MGI:5438795

cx3

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/Fgf14⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * CBA * FVB/N

nervous system

abnormal dentate gyrus morphology ( J:185792 )

• progressive atrophy of dentate granule cells

hippocampal neuron degeneration ( J:185792 )

• progressive atrophy of hippocampal pyramidal neurons

Genotype
MGI:5511058

cx4

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Fgf14^{Tg(tetO-MAPT*P301L)4510Kha}/Fgf14⁺
• Genetic Background: involves: FVB/N

behavior/neurological

decreased exploration in new environment ( J:102973 )

• reduction in exploration in open-field tests

abnormal spatial reference memory ( J:102973 )

• 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

limb grasping ( J:102973 )

• clasping and limb retraction when lifted by the tail

dystonia ( J:102973 )

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

impaired coordination ( J:102973 )

• mutants exhibit longer latencies to traverse a beam

impaired swimming ( J:102973 )

• 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

hunched posture ( J:102973 )

• from about 9.5 months of age, the most severely affected mutants develop hunched posture with hindlimb dysfunction and tail rigor

abnormal gait ( J:102973 )

• from about 9.5 months of age, the most severely affected mutants exhibit decreased ambulation

growth/size/body

weight loss ( J:102973 )

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

nervous system

decreased brain weight ( J:102973 )

• 4-7% reduction in brain weight at 4 months of age

forebrain atrophy ( J:102973 )

• atrophy of the forebrain is seen by 5 months of age

neurofibrillary tangles ( J:102973 )

• 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

tau protein deposits ( J:102973 )

• abnormal conformations of tau are present in the hippocampus and neocortex of 2.5-month old mutants

astrocytosis ( J:102973 )

• reactive astrocytes in forebrains of 10 month old mutants

abnormal corticospinal tract morphology ( J:102973 )

• atrophy of the dorsal corticospinal tracts accompanied by loss of neurofilament

neuron degeneration ( J:102973 )

• degeneration in the hippocampus and neocortex is seen in 10 month old mutants

hippocampal neuron degeneration ( J:102973 )

• massive neuronal loss, most apparent in the CA1 region of the hippocampus

abnormal spinal cord morphology ( J:102973 )

• spinal cords appear thinner, however, no decrease in motor neuron density is seen

muscle

dystonia ( J:102973 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:102973
frontotemporal dementia		DOID:9255	OMIM:600274	J:102973