Phenotypes associated with this allele
nervous system
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• amyloid beta deposition in the brains is higher than in controls with only Tg(PSEN1)5Dbo and Tg(APP69ff5)3Dbo at 13-14 months of age
• amyloid beta deposition is seen in the cortical parenchyma and in cortical vessels as cerebral amyloid angiopathy
• concentrations of insoluble amyloid beta40 and amyloid beta42 is higher than in controls at 13-14 months of age but not at 3 months
• despite the increase in amyloid beta deposition, APP processing and levels of amyloid beta degrading enzymes are normal, indicating that the increase is due to a disturbance of lysosomal-mediated amyloid beta clearance
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• amyloid beta deposition is seen in cortical vessels as cerebral amyloid angiopathy
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• activation of astrocytes is enhanced compared to controls with only Tg(PSEN1)5Dbo and Tg(APP69ff5)3Dbo at 1 year of age
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APP695)3Dbo mutation
(3 available)
Tg(PSEN1)5Dbo mutation
(1 available)
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nervous system
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• at 12 and 17 months of age, females have significantly more plaques in the hippocampus compared to males; plaque load increases dramatically with age in mice, particularly in females
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behavior/neurological
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• poor retention latency exhibited in light-dark step through box
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• escape latencies across trial blocks in left-right discrimination learning are elevated and decrease little in comparison to decreased escape latencies exhibited in controls
• required higher trials to reach criterion and committed more errors in comparison to controls
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• increased duration of immobility in Porsolt forced swim test
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• increased irritability in response to touch escape test as compared to control
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• poor nest building ability in comparison to controls
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homeostasis/metabolism
behavior/neurological
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• retention is reduced in passive avoidance tests involving electric shock training to prevent movement from a lighted area to a dark chamber
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• retention of spatial memory in T-water maze tests declines as early as 3 months after acquisition, faster than for transgenics alone
• acquisition of spatial memory in T-water maze tests is normal
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nervous system
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• lower rate of plaque deposition at 3 and 6 months of age but equivalent to controls at 9 months
• higher brain levels of Abeta1-42
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hprt1tm1(Camk2a-APP*Swe*Lon,-MAPT*P301L*R406W)Geno mutation
(0 available);
any
Hprt1 mutation
(1273 available)
Tg(PSEN1)5Dbo mutation
(1 available)
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behavior/neurological
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• at 5 months, mice exhibit impaired social recognition memory compared with control mice
• at 12 months, mice lack social recognition memory unlike control mice
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• impaired at 8 months
• amnesia at 12 months
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• at 12 months, mice exhibit impaired object recognition following spatial displacement compared with control mice
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• mice exhibit higher swim speeds compared with control mice
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• at 12 months, mice fail to exhibit a decline in activity during the day phase unlike control mice
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• at 5 months mice exhibit increased wake time compared with control mice
• at 5 and 12 months, mice exhibit a decrease in rapid eye movement (REM) sleep compared with control mice
• at 5 months, mice exhibit a reduction in nonREM sleep compared with control mice
• at 12 months mice exhibit longer latency to sleep onset compared with control mice
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nervous system
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N |
• mice do not develop fibrillary plaques or tangles
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• mice exhibit a slowing of electroencephalogram compared with control mice
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• mice exhibit faster decay of long term potentiation compared with control mice
• however, post-tetanic potentiation is normal
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APP695)3Dbo mutation
(3 available)
Tg(PSEN1)5Dbo mutation
(1 available)
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nervous system
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N |
• no differences in neuron number in cingulate cortex relative to wild-type
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• amyloid beta deposits found in cortex and hippocampus tissue from 9 and 12 month old mice and increase in number between 10 ans 12 months of age
(J:43788)
• amyloid beta peptides AB1-40 and AB1-42 are codeposited
(J:43788)
• ratio of amyloid beta peptide 40:42 is 1.75:1
(J:87691)
• exhibits a 50% increase in amyloid beta peptide 42
(J:87691)
• immunoreactive amyloid beta deposits are observed in the cingulate cortex in 12 month-old double transgenic mice; deposits are most evident in gray matter of cingulate and enthorhinal cortex, and to lesser extent in non-neuronal layers of the hippocampal formation
(J:100961)
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• associated with dystropic neuritis in cortex and hippocampus
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• dystrophic neuritis associated with reactive gliosis in cortex and hippocampus
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• neurons in cingulate cortex display 3-fold elevation in phosphorylated tumor suppressor protein (pRb) and activated caspase-3 relative to wild-type neurons
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APP695)3Dbo mutation
(3 available)
Tg(Eno2-PTGS2)32Pasi mutation
(0 available)
Tg(PSEN1)5Dbo mutation
(1 available)
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nervous system
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N |
• no differences in neuron number in cingulate cortex relative to wild-type
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• immunoreactive amyloid beta deposits are observed in the cingulate cortex in 12 month-old triple transgenic mice; deposits are most evident in gray matter of cingulare and enthorhinal cortex, and to lesser extent in non-neuronal layers of the hippocampal formation
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation
(5 available)
Tg(PSEN1)5Dbo mutation
(1 available)
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nervous system
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• dense amyloid beta plaques in the cortex and hippocampus, but not in the adrenal medulla
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• amperometric recordings from chromaffin cells stimulated with a 10 second 70 mM potassium pulse indicate that the quantity of catecholamines released during the initiation of the fusion pore is 50% smaller in mutants than in controls
• chromaffin cells exhibit smaller quantal size and faster kinetics of single exocytotic events (45% lower spike half-width, 60% smaller quantal size, 50% lower decay time) and spike feet show 60% smaller quantal size
• mutants, however, exhibit normal innervation by splanchnic cholinergic nerve terminals of chromaffin cells
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homeostasis/metabolism
Allelic
Composition |
Tg(PSEN1)5Dbo/0
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Genetic
Background |
involves: C3H/HeJ * C57BL/6J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(PSEN1)5Dbo mutation
(1 available)
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nervous system
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N |
• no immunoreactive amyloid beta deposits, neuron loss or reactive astrogliosis observed in cortex or hippocampus from 9 or 12 month old mice as compared to double transgenic mice: Tg(APP695)3Dbo/0, Tg(PSEN1)5Dbo/0
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Analysis Tools