homeostasis/metabolism phenotype

• amyloidosis
  • increase in circulating amyloid beta protein levels
  (MGI Ref ID J:186924)

mammalian phenotype

• homeostasis/metabolism phenotype
  • Normal - mutants exhibit normal body weight, blood glucose, plasma insulin levels, nonfasting blood glucose and nonfasting plasma insulin, and normal glucose and insulin tolerance, indicating normal glucose homeostasis and insulin sensitivity
  (MGI Ref ID J:186924)

• nervous system phenotype
  • Normal - striatal volume is similar in both transgenic and wild-type at either 6 or 12 months of age
  (MGI Ref ID J:145530)

nervous system phenotype

• abnormal medium spiny neuron morphology
  • nuclei of medium spiny stellate neurons in both 6 and 12 month old transgenics are smaller and darker than wild-type
  (MGI Ref ID J:145530)

• decreased neuron number
  • numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
  (MGI Ref ID J:145530)

• neuron degeneration
  • numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
  (MGI Ref ID J:145530)
  • reduced neuron density is observed in striatum of 12, but not 6, month old transgenics
  (MGI Ref ID J:145530)

behavior/neurological phenotype

• abnormal spatial learning
  • 6 month old mutants exhibit slower visuospatial learning than control mice
  (MGI Ref ID J:172426)
  • in the visuospatial re-learning test performed at 9, 11, 13, 15, and 18 months of age, mutants exhibit a decrease in the speed of re-learning the task compared to controls
  (MGI Ref ID J:172426)
  • performance in a morris water maze declines between 3 and 12 months of age
  (MGI Ref ID J:160557)
  • severely impaired performance in a morris water maze with much longer latencies to reach a hidden platform
  (MGI Ref ID J:160557)

• convulsive seizures
  • Background Sensitivity - premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background
  (MGI Ref ID J:227541)

• impaired contextual conditioning behavior
  • Normal - 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the contextual fear conditioning tests
  (MGI Ref ID J:234430)
  • Normal - 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in contextual conditioning behavior
  (MGI Ref ID J:234430)
  • Normal - however, VO-OHpic treatment does not affect auditory-cued fear conditioning (hippocampal-independent task), exploratory activity or basal freezing behavior
  (MGI Ref ID J:234430)
  • mice exhibit decreased freezing to context
  (MGI Ref ID J:234430)

• impaired passive avoidance behavior
  (MGI Ref ID J:160557)

• impaired spatial learning
  • Normal - 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the novel object-location task
  (MGI Ref ID J:234430)
  • Normal - 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in spatial learning tasks
  (MGI Ref ID J:234430)
  • mice exhibit impaired behavior in the novel object location task
  (MGI Ref ID J:234430)

homeostasis/metabolism phenotype

• amyloid beta deposits
  (MGI Ref ID J:160557)
  • at 2 months of age carriers are indistinguishable from C57BL/6J controls, but at 4 months of age very small plaques are found in the cortex, and at 6 months of age plaques are evident in the cortex and hippocampus
  (MGI Ref ID J:208080)
  • Background Sensitivity - there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background
  (MGI Ref ID J:227541)

mammalian phenotype

• taste/olfaction phenotype
  • Normal - mutants do not exhibit Alzheimer's disease-related impairments in olfactory performance in tests based on an operant conditioning procedure and in tests based on a habituation/dishabituation procedure
  (MGI Ref ID J:172426)

mortality/aging

• premature death
  • about 40% of mice are lost by 12 months of age
  (MGI Ref ID J:160557)

nervous system phenotype

• abnormal CNS synaptic transmission
  • basal synaptic transmission is lower in hippocampal slices
  (MGI Ref ID J:234430)
  • VO-OHpic treatment does not rescue the lower basal synaptic transmission
  (MGI Ref ID J:234430)

• amyloid beta deposits
  (MGI Ref ID J:160557)
  • at 2 months of age carriers are indistinguishable from C57BL/6J controls, but at 4 months of age very small plaques are found in the cortex, and at 6 months of age plaques are evident in the cortex and hippocampus
  (MGI Ref ID J:208080)
  • Background Sensitivity - there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background
  (MGI Ref ID J:227541)

• astrocytosis
  (MGI Ref ID J:160557)

• axon degeneration
  • axon degeneration and synapse loss
  (MGI Ref ID J:160557)

• convulsive seizures
  • Background Sensitivity - premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background
  (MGI Ref ID J:227541)

• reduced long term potentiation
  • Normal - semi-chronic treatment with VO-OHpic fully rescues LTP levels in hippocampal slices
  (MGI Ref ID J:234430)

behavior/neurological phenotype

• convulsive seizures
  • Normal - despite the increased lethal seizures, the electroconvulsive threshold is not decreased relative to DBA/2J controls
  (MGI Ref ID J:227541)
  • Background Sensitivity - on the DBA/2J background hemizygotes that die prematurely are found in a lethal seizure pose of clenched front limbs and stretched out hind limbs consistent with the audiogenic seizure-induced death inherent in DBA/2J, but the percentage of hemizygotes found dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
  (MGI Ref ID J:227541)
  • Background Sensitivity - und dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
  (MGI Ref ID J:227541)

nervous system phenotype

• amyloid beta deposits
  • Background Sensitivity - although hemizygotes do have some ThioS+ plaque deposition in the cortex, there are far fewer plaques than are found in hemizygotes on the C57BL/6J background (average 10 per section versus 58 per section)
  (MGI Ref ID J:227541)

• convulsive seizures
  • Normal - despite the increased lethal seizures, the electroconvulsive threshold is not decreased relative to DBA/2J controls
  (MGI Ref ID J:227541)
  • Background Sensitivity - on the DBA/2J background hemizygotes that die prematurely are found in a lethal seizure pose of clenched front limbs and stretched out hind limbs consistent with the audiogenic seizure-induced death inherent in DBA/2J, but the percentage of hemizygotes found dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
  (MGI Ref ID J:227541)
  • Background Sensitivity - und dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
  (MGI Ref ID J:227541)

• microgliosis
  • cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls
  (MGI Ref ID J:227541)

hematopoietic system phenotype

• microgliosis
  • cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls
  (MGI Ref ID J:227541)

homeostasis/metabolism phenotype

• amyloid beta deposits
  • Background Sensitivity - although hemizygotes do have some ThioS+ plaque deposition in the cortex, there are far fewer plaques than are found in hemizygotes on the C57BL/6J background (average 10 per section versus 58 per section)
  (MGI Ref ID J:227541)

immune system phenotype

• microgliosis
  • cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls
  (MGI Ref ID J:227541)

mammalian phenotype

• nervous system phenotype
  • Normal - no significant differences are found between hemizygotes and DBA/2J in neuron number in the three different regions of the cortex at 6 months of age, indicating no increase in neuronal cell loss, and the number of cortical astrocytes is normal
  (MGI Ref ID J:227541)

mortality/aging

• premature death
  • There is a much higher rate of premature death in hemizygotes on the DBA/2J background than on the C57BL/6J background, although hemizygotes that survive beyond 6 months of age do not have a high rate of premature death thereafter
  (MGI Ref ID J:227541)

behavior/neurological phenotype

• convulsive seizures
  • Background Sensitivity - despite the presence of functional hemolytic complement these mice have the same rate of lethal seizures as transgenics with the non-functional DBA/2J allele
  (MGI Ref ID J:227541)

homeostasis/metabolism phenotype

• amyloid beta deposits
  • Background Sensitivity - the complement pathway does not impact plaque deposition in the cortex, the number of plaques is the same as that in transgene carriers with the DBA/2J allele of Hc
  (MGI Ref ID J:227541)

mammalian phenotype

• nervous system phenotype
  • Normal - no significant differences are found in cortical neuron number in complement deficient versus functional transgene carriers
  (MGI Ref ID J:227541)

mortality/aging

• premature death
  (MGI Ref ID J:227541)

nervous system phenotype

• amyloid beta deposits
  • Background Sensitivity - the complement pathway does not impact plaque deposition in the cortex, the number of plaques is the same as that in transgene carriers with the DBA/2J allele of Hc
  (MGI Ref ID J:227541)

• convulsive seizures
  • Background Sensitivity - despite the presence of functional hemolytic complement these mice have the same rate of lethal seizures as transgenics with the non-functional DBA/2J allele
  (MGI Ref ID J:227541)

behavior/neurological phenotype

• abnormal olfactory behavior
  • in the buried food test, mice need more time to find the hidden food than wild-type mice indicating impaired olfactory performance
  (MGI Ref ID J:275175)
  • in the olfactory discrimination test, mice show decreases in the numbers of correct olfactory discrimination responses per trial at 3-4 months, 6-7 months, and 9-10 months of age
  (MGI Ref ID J:275175)

• abnormal spatial reference memory
  • in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice require longer to find the platform, indicating that spatial memory impairments begin at 6-7 months of age
  (MGI Ref ID J:275175)

• impaired spatial learning
  • in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice show decreased crossing plate times in the probe trial indicating that spatial discrimination learning impairments begin at 6-7 months of age
  (MGI Ref ID J:275175)

homeostasis/metabolism phenotype

• amyloid beta deposits
  • mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age
  (MGI Ref ID J:275175)

nervous system phenotype

• abnormal action potential
  • mitral cells in 3-4 and 9-10 month old mice exhibit a higher spontaneous firing rate of spontaneous action potential indicating the hyperactivation of mitral cells
  (MGI Ref ID J:275175)

• abnormal asymmetric synapse morphology
  • the presynaptic and postsynaptic membrane structures of asymmetric synapses (excitatory synapses) in the olfactory bulb are damaged
  (MGI Ref ID J:275175)

• abnormal olfactory bulb external plexiform layer morphology
  • Normal - however, laminar organization of the olfactory bulb is normal
  (MGI Ref ID J:275175)
  • mice exhibit a wider synaptic cleft in the external plexiform layer
  (MGI Ref ID J:275175)

• abnormal olfactory bulb granule cell morphology
  • the dendritic spine density of granule cells is reduced in the olfactory bulb
  (MGI Ref ID J:275175)

• abnormal postsynaptic density morphology
  • thickness of the postsynaptic density in olfactory bulb asymmetric synapses is thinner in 3-4, 6-7, and 9-10 month old mice
  (MGI Ref ID J:275175)

• abnormal symmetric synapse morphology
  • mice exhibit a wider synaptic cleft in the external plexiform layer of symmetric synapses
  (MGI Ref ID J:275175)

• abnormal synapse morphology
  (MGI Ref ID J:275175)

• abnormal synaptic transmission
  • 3-4 and 9-10 month old mice exhibit increased gamma, low-gamma, and high-gamma oscillations and firing rates of mitral cells in the olfactory bulb external plexiform layer
  (MGI Ref ID J:275175)
  • Normal - local application of the GABA(A)R agonist muscimol nearly abolishes the aberrant increase in gamma oscillations in the external plexiform layer at advanced stages of disease while a GABA(A)R antagonist bicuculline increased the gamma oscillations
  (MGI Ref ID J:275175)

• abnormal synaptic vesicle morphology
  • synaptic vesicles of olfactory bulb asymmetric synapses exhibit unclear and broken membrane structure and blurred boundaries at 6-7 and 9-10 months of age
  (MGI Ref ID J:275175)

• amyloid beta deposits
  • mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age
  (MGI Ref ID J:275175)

• decreased dendritic spine density
  • immature spine density tends to decline at 3-4 and 6-7 months of age and is reduced at 9-10 months of age
  (MGI Ref ID J:275175)
  • mature spine density is the same as in wild-type mice at 3-4 months of age but is decreased in 6-7 and 9-10 month old mice
  (MGI Ref ID J:275175)
  • the dendritic spine density of granule cells is reduced in the olfactory bulb
  (MGI Ref ID J:275175)

behavior/neurological phenotype

• abnormal spatial reference memory
  • 13 month old transgenic mice commit more errors in the water maze than controls, at 7 months of age both groups test similarly
  (MGI Ref ID J:139071)
  • transgenic mice exhibit a 4-5% higher preference for the arm of the radial arm water maze that held the platform on the previous day
  (MGI Ref ID J:139071)

• impaired coordination
  • 14 month old transgenic mice exhibit a reduced ability to maintain balance on a rotarod
  (MGI Ref ID J:139071)

growth/size/body region phenotype

• decreased body weight
  • at 14 months, transgenics weigh less than controls
  (MGI Ref ID J:139071)

homeostasis/metabolism phenotype

• amyloid beta deposits
  • deposits observed in hippocampus by 6 months of age
  (MGI Ref ID J:139071)
  • occasional deposits can be found in mice as young as 6 months of age
  (MGI Ref ID J:87691)
  • plaques are abundant in hippocampus and cortex by 9 months of age
  (MGI Ref ID J:87691)
  • ratio of amyloid beta peptide 40:42 is 0.50:1
  (MGI Ref ID J:87691)

nervous system phenotype

• amyloid beta deposits
  • deposits observed in hippocampus by 6 months of age
  (MGI Ref ID J:139071)
  • occasional deposits can be found in mice as young as 6 months of age
  (MGI Ref ID J:87691)
  • plaques are abundant in hippocampus and cortex by 9 months of age
  (MGI Ref ID J:87691)
  • ratio of amyloid beta peptide 40:42 is 0.50:1
  (MGI Ref ID J:87691)

• reduced long term potentiation
  • transient long term potentiation (t-LTP) is reduced in transgenics and is age-independent
  (MGI Ref ID J:139071)

behavior/neurological phenotype

• abnormal spatial learning
  • transgenic mice fed sucrose water failed to learn Morris water maze test after 5 days of training
  (MGI Ref ID J:129021)
  • water-fed transgenic mice retained some learning ability over 5 day test period, but did not perform as well in the water maze test as non-transgenic controls
  (MGI Ref ID J:129021)

• increased fluid intake
  • mice fed sucrose water exhibited increased water consumption
  (MGI Ref ID J:129021)

nervous system phenotype

• amyloid beta deposits
  • amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
  (MGI Ref ID J:129021)
  • deposits are more extensive in females
  (MGI Ref ID J:113199)
  • exhibits an overall increase in soluble and insoluble amyloid beta peptide 40 and 42 between 4 and 12 months
  (MGI Ref ID J:113200)
  • insoluble amyloid beta42 is increased 2-fold in cerebrum of sucrose-fed mice as compared to water-fed control
  (MGI Ref ID J:129021)
  • level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age
  (MGI Ref ID J:113199)
  • plaques are restricted to cortex and hippocampus at time points up to 12 months of age
  (MGI Ref ID J:113200)
  • plaques increase in number and size over time
  (MGI Ref ID J:113200)
  • senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months of age
  (MGI Ref ID J:113200)
  • sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks
  (MGI Ref ID J:113199)
  • total amyloid beta levels are increased by 3.6 fold in sucrose fed mice
  (MGI Ref ID J:129021)

• cerebral amyloid angiopathy
  • amyloid deposition is observed in leptomeningeal vasculature
  (MGI Ref ID J:113200)
  • exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
  (MGI Ref ID J:113200)

cardiovascular system phenotype

• vasculature congestion
  (MGI Ref ID J:113200)

growth/size/body region phenotype

• increased body weight
  • mice fed sucrose water consistently gained weight over study time period (2 months- 8 months)
  (MGI Ref ID J:129021)
  • sucrose-fed mice increased body weight by 17% over water-fed controls
  (MGI Ref ID J:129021)

homeostasis/metabolism phenotype

• amyloid beta deposits
  • amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
  (MGI Ref ID J:129021)
  • deposits are more extensive in females
  (MGI Ref ID J:113199)
  • exhibits an overall increase in soluble and insoluble amyloid beta peptide 40 and 42 between 4 and 12 months
  (MGI Ref ID J:113200)
  • insoluble amyloid beta42 is increased 2-fold in cerebrum of sucrose-fed mice as compared to water-fed control
  (MGI Ref ID J:129021)
  • level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age
  (MGI Ref ID J:113199)
  • plaques are restricted to cortex and hippocampus at time points up to 12 months of age
  (MGI Ref ID J:113200)
  • plaques increase in number and size over time
  (MGI Ref ID J:113200)
  • senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months of age
  (MGI Ref ID J:113200)
  • sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks
  (MGI Ref ID J:113199)
  • total amyloid beta levels are increased by 3.6 fold in sucrose fed mice
  (MGI Ref ID J:129021)

• amyloidosis
  (MGI Ref ID J:129021)

• cerebral amyloid angiopathy
  • amyloid deposition is observed in leptomeningeal vasculature
  (MGI Ref ID J:113200)
  • exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
  (MGI Ref ID J:113200)

• impaired glucose tolerance
  • mice fed sucrose water displayed an impaired glucose tolerance as compared to water-fed control
  (MGI Ref ID J:129021)

• increased circulating cholesterol level
  • total cholesterol, but not HDL, levels are increased 30% in mice fed sucrose water as compared to water-fed control
  (MGI Ref ID J:129021)

• increased circulating insulin level
  • fasting plasma insulin levels are increased 3 fold in mice fed sucrose water as compared to water-fed control
  (MGI Ref ID J:129021)

• increased circulating triglyceride level
  • elevated plasma triglyceride levels observed in females at 15 weeks of age
  (MGI Ref ID J:113199)