Phenotypes Associated with This Genotype

Genotype
MGI:5828490

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-MAPT*A152T)L1Lms/0
• Genetic Background: B6.Cg-Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*A152T)L1Lms

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

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:233816 )

• in response to pentylenetetrazol (PTZ), spike counts increase faster and reach higher levels in mutants than in controls, indicating a lowered threshold for chemically induced seizures

impaired spatial learning ( J:233816 )

• mice show age-dependent impairments in learning and memory in the Morris water maze

• at 4-6 months of age, mutants learn the task more poorly than controls but show no memory retention deficits in a probe trial 24 hours after the last training trial

• at 7-9 and 11-14 months of age, mutants do not differ from controls in task acquisition and memory retention testsat 7-9 and 11-14 months of age, mutants do not differ from controls in task acquisition and memory retention tests

• at 17-19 months, mutants show impaired learning, taking longer to reach the original platform location in the probe trial, do not cross the target location more often than equivalent locations in nontarget quadrants

abnormal nest building behavior ( J:233816 )

• mice show impairments in nest building behavior at 10-14 months of age and old mice show a trend in the same direction

• however, mice show normal social interaction, normal exploratory behavior and no anxiety related behaviors

growth/size/body

decreased body weight ( J:233816 )

• adults weigh slightly less than controls

nervous system

increased susceptibility to pharmacologically induced seizures ( J:233816 )

• in response to pentylenetetrazol (PTZ), spike counts increase faster and reach higher levels in mutants than in controls, indicating a lowered threshold for chemically induced seizures

astrocytosis ( J:233816 )

• astrocytosis in the brain by 4 months of age

• treatment with doxycycline for 2 months, starting at 6 months of age, reverses astocytosis

abnormal brain morphology ( J:233816 )

• cortical and hippocampal levels of human Tau fragments are lower than in mice expressing wild-type human MAPT

• accumulation of misfolded, nonfilamentous soluble tau in neurons

• however, dense neuronal tau inclusions are not seen in 8, 20, or 23 month old mutants

• mice treated with doxycycline for 2 months, starting at 6 months of age show suppression of tau accumulation in neurons

hippocampal neuron degeneration ( J:233816 )

• mice at 20-23 months of age, but not at 4-6 months of age, show neuronal loss in dentate gyrus and CA3 but not in CA1

abnormal brain wave pattern ( J:233816 )

• EEGs in 4-9 month old mice indicated that at baseline, epileptiform spikes are more abundant than in controls

abnormal CNS synaptic transmission ( J:233816 )

• mossy fiber synapse between dentate granule cells and CA3 pyramidal neurons exhibits a steeper slope of the input/output curve when fEPSPs are induced, indicating increased synaptic transmission strength at 4-8 months of age, with further increase in strength at 20 months

decreased paired-pulse facilitation ( J:233816 )

• paired-pulse ratio is lower at 20 months, but not a 4-8 months, of age indicating reduced paired-pulse facilitation

• however, mossy fiber long-term potentiation is unchanged at old age

mortality/aging

mortality/aging ( J:233816 )

N • mice survive into old age

cellular

astrocytosis ( J:233816 )

• astrocytosis in the brain by 4 months of age

• treatment with doxycycline for 2 months, starting at 6 months of age, reverses astocytosis