Mouse Genome Informatics
cn1
    Lrp1tm2Her/Lrp1tm2Her
Tg(APP695)3Dbo/0
Tg(PSEN1)5Dbo/0
Tg(Tagln-cre)1Her/0

involves: 129S7/SvEvBrd * C3H/HeJ * C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• amyloid beta deposition is seen in cortical vessels as cerebral amyloid angiopathy
• activation of astrocytes is enhanced compared to controls with only Tg(PSEN1)5Dbo and Tg(APP69ff5)3Dbo at 1 year of age
• 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

other phenotype
• amyloid beta deposition is seen in cortical vessels as cerebral amyloid angiopathy
• 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


Mouse Genome Informatics
cx2
    Tg(APP695)3Dbo/0
Tg(PSEN1)5Dbo/0

B6.Cg-Tg(APP695)3Dbo Tg(PSEN1)5Dbo
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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

behavior/neurological
• increased duration of immobility in Porsolt forced swim test
• poor retention latency exhibited in light-dark step through box
• 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
• increased irritability in response to touch escape test as compared to control
• poor nest building ability in comparison to controls

other phenotype
• 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

integument
• increased irritability in response to touch escape test as compared to control


Mouse Genome Informatics
cx3
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system

other phenotype

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:157228


Mouse Genome Informatics
cx4
    Sorl1tm1Tew/Sorl1tm1Tew
Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129 * C3H/HeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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

other phenotype
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:142501


Mouse Genome Informatics
cx5
    Tlr2tm1Kir/Tlr2tm1Kir
Tg(APP695)3Dbo/?
Tg(PSEN1)5Dbo/?

involves: 129 * C3H/HeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• retention is reduced in passive avoidance tests involving electric shock training to prevent movement from a lighted area to a dark chamber
• 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

nervous system
• 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

other phenotype
• 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


Mouse Genome Informatics
cx6
    Klc1tm1Gsn/Klc1+
Tg(APP695)3Dbo/?

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• increased axonal swelling independent of amyloid deposition
• levels of amyloid beta are consistently elevated relative to controls

other phenotype
• levels of amyloid beta are consistently elevated relative to controls

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:96346


Mouse Genome Informatics
cx7
    Bace1tm1Pcw/Bace1tm1Pcw
Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice perform as well as control mice in platform and probe trials in Morris water maze tasks (J:123534)
• in open field test, mice are similar to Bace1tm1Pcw homozygotes, and spend more time in open area at center of field than at periphery
• swim speed is lower than other genotypes and nontransgenic mice in hidden and visible platform trials

nervous system
N
• in 12- or 20-month old mice, no amyloid beta (Abeta) aggregation is detected in brains; no amyloid deposits are found (J:123534)


Mouse Genome Informatics
cx8
    Bace1tm1Pcw/Bace1+
Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice are significantly impaired in Morris water maze tasks

nervous system
• high level of amyloid beta aggregates are found in brain at 12 months of age

other phenotype
• in 12-month old brains, there is a 27% reduction in amyloid beta aggregates compared to transgenic mice that are wild-type for Bace1; there are no significant differences at 20 months
• in 12-month old brains, there is 37% reduction in percentage of brain volume occupied by amyloid beta deposits, but no difference at 20 months
• high level of amyloid beta aggregates are found in brain at 12 months of age


Mouse Genome Informatics
cx9
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• 16-18 month-old mice swim farther to find platform and spend less time in platform vicinity than controls

nervous system
• 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

other phenotype
• mice display amyloid beta aggregates at 12 and 20 months
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:123534
Alzheimer Disease; AD 104300 J:123534


Mouse Genome Informatics
cx10
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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)

other phenotype
• 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)


Mouse Genome Informatics
cx11
    Tg(APP695)3Dbo/0
Tg(PSEN1)5Dbo/0

involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• no differences in neuron number in cingulate cortex relative to wild-type (J:100961)
• associated with dystropic neuritis in cortex and hippocampus
• dystrophic neuritis associated with reactive gliosis in cortex and hippocampus
• 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)
• neurons in cingulate cortex display 3-fold elevation in phosphorylated tumor suppressor protein (pRb) and activated caspase-3 relative to wild-type neurons

other phenotype
• 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)


Mouse Genome Informatics
cx12
    Tg(APP695)3Dbo/0
Tg(Eno2-PTGS2)32Pasi/0
Tg(PSEN1)5Dbo/0

involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• no differences in neuron number in cingulate cortex relative to wild-type (J:100961)
• 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

other phenotype
• 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


Mouse Genome Informatics
cx13
    Tg(APP695)3Dbo/0
Tg(PSEN1)S8-4Dbo/0

involves: C57BL/6J * C3H/HeJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
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 (J:43788)


Mouse Genome Informatics
cx14
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
• 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

vision/eye
• 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
• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
• thioflavine-S positive plaques are first observed in females in the IPL at 12 months
• 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 OPL at 12 months
• plaques are first observed in males at 13 months
• 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

immune system
• 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

other phenotype
• 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

hematopoietic system
• 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


Mouse Genome Informatics
tg15
    Tg(APP695)3Dbo/0
B6.C3-Tg(APP695)3Dbo
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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

behavior/neurological
• at 24 months, males display a mild deterioration of sensorimotor abilities
• mice backcrossed 10 generations have higher reactivity to acoustic stimuli compared to wild-type
• 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

other phenotype
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 4 606889 J:109847
Alzheimer Disease; AD 104300 J:109847


Mouse Genome Informatics
tg16
    Tg(APP695)3Dbo/0
involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
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 (J:43788)
• 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)

other phenotype
• 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)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:87691