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
    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
cx4
    Hprttm1(Camk2a-APP*Swe*Lon,-MAPT*P301L*R406W)Geno/Hprt+
Tg(PSEN1)5Dbo/0

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 5 months, mice exhibit impaired social recognition memory compared with control mice (J:180977)
• at 12 months, mice lack social recognition memory unlike control mice (J:180977)
• amnesia at 12 months (J:180977)
• impaired at 8 months (J:180977)
• at 12 months, mice exhibit impaired object recognition following spatial displacement compared with control mice (J:180977)
• impaired at 12 months (J:180977)
• mice exhibit higher swim speeds compared with control mice (J:180977)
• at 12 months, mice fail to exhibit a decline in activity during the day phase unlike control mice (J:180977)
• at 5 months mice exhibit increased wake time compared with control mice (J:180977)
• at 5 and 12 months, mice exhibit a decrease in rapid eye movement (REM) sleep compared with control mice (J:180977)
• at 5 months, mice exhibit a reduction in nonREM sleep compared with control mice (J:180977)
• at 12 months mice exhibit longer latency to sleep onset compared with control mice (J:180977)

nervous system
N
• mice do not develop fibrillary plaques or tangles (J:180977)
• mice exhibit a slowing of electroencephalogram compared with control mice (J:180977)
• mice exhibit faster decay of long term potentiation compared with control mice (J:180977)
• however, post-tetanic potentiation is normal (J:180977)

homeostasis/metabolism
• mice exhibit early and progressive brain glucose metabolism compared with control mice (J:180977)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:180977


Mouse Genome Informatics
cx5
    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
cx6
    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
cx7
    Tg(APPSWE)2576Kha/0
Tg(PSEN1)5Dbo/0

involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• dense amyloid beta plaques in the cortex and hippocampus, but not in the adrenal medulla
• 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

homeostasis/metabolism
• chromaffin cells release 50% less catecholamine (mean quantal content released per vesicle is halved) in response to a 10 second 70 mM potassium pulse

other phenotype
• dense amyloid beta plaques in the cortex and hippocampus, but not in the adrenal medulla

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:191088


Mouse Genome Informatics
tg8
    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 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 (J:43788)