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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APP695)3Dbo mutation
(3 available)
Tg(PSEN1dE9)S9Dbo mutation
(1 available)
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nervous system
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:
Sorl1tm1Tew mutation
(0 available);
any
Sorl1 mutation
(131 available)
Tg(APP695)3Dbo mutation
(3 available)
Tg(PSEN1dE9)S9Dbo mutation
(1 available)
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nervous system
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• amyloid beta levels and amyloid plaque burden are increased at 4.5 and 6 months of age, but not at 12 months of age, compared to transgenic mice wild-type for Sorl1 suggesting an acceleration in accumulation of amyloid beta
• some of the largest differences in amyloid measures are detected in the cerebellum
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homeostasis/metabolism
Allelic
Composition |
Klc1tm1Gsn/Klc1+
Tg(APP695)3Dbo/?
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Genetic
Background |
involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6 |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Klc1tm1Gsn mutation
(1 available);
any
Klc1 mutation
(54 available)
Tg(APP695)3Dbo mutation
(3 available)
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nervous system
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• levels of amyloid beta are consistently elevated relative to controls
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• increased axonal swelling independent of amyloid deposition
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homeostasis/metabolism
behavior/neurological
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N |
• mice perform as well as control mice in platform and probe trials in Morris water maze tasks
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• in open field test, mice are similar to Bace1tm1Pcw homozygotes, and spend more time in open area at center of field than at periphery
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• swim speed is lower than other genotypes and nontransgenic mice in hidden and visible platform trials
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nervous system
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N |
• in 12- or 20-month old mice, no amyloid beta (Abeta) aggregation is detected in brains; no amyloid deposits are found
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behavior/neurological
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• mice are significantly impaired in Morris water maze tasks
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nervous system
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• high level of amyloid beta aggregates are found in brain at 12 months 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(PSEN1dE9)S9Dbo mutation
(1 available)
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behavior/neurological
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• mice travel shorter distance in open-field and show less activity or excursions into central area; mice remain near periphery of apparatus rather than entering open center of field
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• 16-18 month-old mice swim farther to find platform and spend less time in platform vicinity than controls
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nervous system
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• one month following neuron injection with virus expressing short hairpin RNA to silence Bace1, there is a 38% reduction in amyloid beta burden in hippocampus compared to uninjected hippocampus
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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(APP695)3Dbo mutation
(3 available)
Tg(PSEN1dE9)S9Dbo mutation
(1 available)
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nervous system
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• develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus
(J:87691)
• ratio of amyloid beta peptide 40:42 is 0.75:1
(J:87691)
• 150% increase in amyloid beta peptide 42
(J:87691)
• at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex
(J:104236)
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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)S8-4Dbo mutation
(0 available)
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nervous system
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N |
• no immunoreactive amyloid beta deposits found 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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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APP695)3Dbo mutation
(3 available)
Tg(PSEN1dE9)S9Dbo mutation
(1 available)
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nervous system
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• increase in microglial cell activity in retina is observed in 12-15 month old transgenics
• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
• microglia density, but not cell body size, is increased in transgenics
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• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
• plaques have radial branches with a central core
• plaque size ranges from 5-20 um, larger plaques are observed at 15-16 months
• plaques appear earlier in females than in males and increase in number over time
• 100% of females and 75% of males have plaques in retina by 15-16 months
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• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
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vision/eye
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• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
• most plaques (34.7% and 41% respectively) are found in the inner and outer plexiform layers
• thickness of the retinal nuclear layers is similar to control, suggesting that there is no obvious neuronal cell loss
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• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
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• plaques are first observed in males at 13 months
• plaques are embedded within IPL cholinergic bands
• thioflavine-S positive plaques are first observed in females in the IPL at 12 months
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• thioflavine-S positive plaques are first observed in females in the OPL at 12 months
• plaques are first observed in males at 13 months
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• amplitudes of a and b waves are decreased in 12-16 month old mice when tested at lower light intensity, but not a higher intensity
• latency and implicit time as determined by ERG measurement are similar to control
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immune system
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• increase in microglial cell activity in retina is observed in 12-15 month old transgenics
• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
• microglia density, but not cell body size, is increased in transgenics
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hematopoietic system
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• increase in microglial cell activity in retina is observed in 12-15 month old transgenics
• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
• microglia density, but not cell body size, is increased in transgenics
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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)
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nervous system
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• in mice 26 months old, moderate levels of amyloid deposits in brains are observed in mice backcrossed 5-7 generations
• mice 12-13 months old that have been backcrossed 10 generations have slightly higher accumulations than Tg(APP695)3Dbo mice
• old (<24 months) animals backcrossed either 5-7 or 10 times to B6 have significantly higher levels of amyloid Abeta in their brains than adult (~9.6 months) or middle aged (13-15 months) animals
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behavior/neurological
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• at 24 months, males display a mild deterioration of sensorimotor abilities
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• mice backcrossed 10 generations have higher reactivity to acoustic stimuli compared to wild-type
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• in radial maze testing, male mutants backcrossed 5-7 generations show high motor reactivity compared to females or control animals, and entered the closest arm of the maze which prevented them from learning the task
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homeostasis/metabolism
Allelic
Composition |
Tg(APP695)3Dbo/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(APP695)3Dbo mutation
(3 available)
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nervous system
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N |
• no immunoreactive amyloid beta deposits found in cortex or hippocampus from 12 month old mice as compared to double transgenic mice: Tg(APP695)3Dbo/0, Tg(PSEN1)5Dbo/0
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• amyloid beta deposits observed in cortex and hippocampus of 18 and 20 month old mice
(J:43788)
• ratio of amyloid beta peptide 40:42 is 3:1
(J:87691)
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homeostasis/metabolism
Analysis Tools