behavior/neurological phenotype

• impaired contextual conditioning behavior
  • associative learning in contextual fear conditioning is impaired in 6-week induced mice, with mice spending less time freezing after training than wild-type mice
  (MGI Ref ID J:177847)

growth/size/body region phenotype

• decreased body weight
  • transgenic mice with transgene expression induced by removal of doxycycline from their food 4-6 weeks postnatal exhibit a slightly decreased body weight compared to control littermates
  (MGI Ref ID J:104240)

homeostasis/metabolism phenotype

• amyloid beta deposits
  • mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit amyloid beta deposits in the hippocampus
  (MGI Ref ID J:177847)

nervous system phenotype

• abnormal forebrain morphology
  • lts are found at 27 weeks of induction
  (MGI Ref ID J:104240)
  • in transgenic mice induced for 8 and 12 weeks, there is an increase in aggregations of tau protein (insoluble tau) with an increased amount of phosphorylated tau present; at 15 weeks, there is less soluble tau than in wild-type forebrains and similar results are found at 27 weeks of induction
  (MGI Ref ID J:104240)

• abnormal hippocampus morphology
  • brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the hippocampus compared to controls
  (MGI Ref ID J:104240)

• amyloid beta deposits
  • mice with transgene expression induced by removal of doxycycline from the food 4-6 weeks postnatal exhibit amyloid beta deposits in the hippocampus
  (MGI Ref ID J:177847)

• forebrain atrophy
  • induced transgenic mice at 12 weeks postnatal display significant forebrain atrophy with decrease in forebrain mass
  (MGI Ref ID J:104240)

• gliosis
  • reactive astrogliosis is increased throughout the cortex and hippocampus of mutants evident by an increase in radial and stellate-shaped astrocytes
  (MGI Ref ID J:104240)

• hippocampal neuron degeneration
  • 50% reduction in the number of NeuN-positive cells in hippocampal area CA1 in 6-week induced mice
  (MGI Ref ID J:177847)

• neurofibrillary tangles
  • other methosds also identify neurofibrillary tangle-like structures in the cerebral cortex, hippocampus and entorhinal cortex of transgenic mice
  (MGI Ref ID J:104240)
  • ic mice but not wild-type
  (MGI Ref ID J:104240)
  • brains of transgenic mice induced for 8 or 12 weeks do not express markers for late stage tangles similar to what is observed in wild-type
  (MGI Ref ID J:104240)
  • neurofibrillary tangle-like pathology is exhibited in brains of transgenic mice induced for 27 weeks; there are numerous intraneuronal and flame-shaped neurons positive for neurofibrillary tangle-specific proteins in the cortex and hippocampus of transgenic mice but not wild-type
  (MGI Ref ID J:104240)

• thin cerebral cortex
  • whereas wild-type or non-induced transgenic mice had the same neuronal density
  (MGI Ref ID J:104240)
  • brains of transgenic mice induced for 12 weeks show a significant decrease in thickness and neuronal density in the cerebral cortex compared to controls; mice induced for 8 or 12 weeks show a 25 or 40% decrease in cortical neuronal density, respectively, whereas wild-type or non-induced transgenic mice had the same neuronal density
  (MGI Ref ID J:104240)

• abnormal synapse morphology
  • mice exhibit reduced density of synaptophysin puncta in the stratum radiatum of the hippocampus, indicating reduced synapse density following a 6-week induction
  (MGI Ref ID J:177847)

• decreased brain weight
  • transgenic mice with induction of expression of the transgene for different time periods display progressive decrease in brain weight; with induction for 5 weeks there is a 15-20% decrease in brain weight and with more than 12 weeks of induction, the weight decrease is 30%
  (MGI Ref ID J:104240)(MGI Ref ID J:177847)
  • ht decrease is 30%
  (MGI Ref ID J:104240)

• astrocytosis
  • reactive astrogliosis is seen in the cortex and hippocampus in 6-week induced mice
  (MGI Ref ID J:177847)

• impaired synaptic plasticity
  • mice exhibit impaired synaptic plasticity following a 6-week induction
  (MGI Ref ID J:177847)

• reduced long term potentiation
  • mice exhibit diminished CA1 long term potentiation (LTP) following a 6-week induction
  (MGI Ref ID J:177847)

normal phenotype

• no abnormal phenotype detected
  • Normal - hemizygous mice are viable, fertile, show normal size and display no behavioral abnormalities; homozygosity may be lethal
  (MGI Ref ID J:104240)