Phenotypes Associated with This Genotype

Genotype
MGI:5511058

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

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

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