Mouse Genome Informatics
cx1
    Qpcttm1.2Tbay/Qpcttm1.2Tbay
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0

B6.Cg-Qpcttm1.2Tbay Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at 6 months, mice exhibit a lower plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

behavior/neurological
N
• spatial working memory defects observed in Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice are rescued (J:169481)
• mice exhibit improved motor coordination on a beam or when suspended by a string compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice (J:169481)

homeostasis/metabolism
• at 6 months, mice exhibit a lower plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice


Mouse Genome Informatics
cx2
    Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
Tg(Thy1-QPCT)#Tbay/0

B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas Tg(Thy1-QPCT)#Tbay
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice exhibit decreased alternation frequency in a Y maze compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice
• mice exhibit impaired motor coordination on a beam or when suspended by a string compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

nervous system
• at 6 months, mice exhibit a higher plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

homeostasis/metabolism
• at 6 months, mice exhibit a higher plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice


Mouse Genome Informatics
cx3
    Apoa4tm1Bres/Apoa4tm1Bres
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?

involves: 129S4/SvJae * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• impaired survival compared to wild-type mice and transgenic mice wild-type for Apoa4

nervous system
• accelerated deposition compared to transgenic mice wild-type for Apoa4
• large pyramidal neurons in cortical layer 5 and neurons in hippocampus contain more disrupted morphologies indicating enhanced neuron loss compared to transgenic mice wild-type for Apoa4
• loss of neurons is increased in areas of the cortex and CA1, CA3 of the hippocampus

behavior/neurological
• impaired spatial learning (slower decrease in escape latency during training in a morris water maze) compared to transgenic mice wild-type for Apoa4
• more time spent in the incorrect quadrant in a probe trial in a morris water maze compared to transgenic mice wild-type for Apoa4

homeostasis/metabolism
• accelerated deposition compared to transgenic mice wild-type for Apoa4

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:169682


Mouse Genome Informatics
cx4
    Cdk5r1tm2.1Lht/?
Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?

involves: 129S4/SvJaeSor * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• long term depression is restored to wild type levels as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas (J:208030)
• anxiety, cognitive performance and contextual/cued fear conditioning are restored to wild type levels as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas (J:208030)

nervous system
N
• presence of reactive astrocytes and activated microglia is close to wild type levels as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas (J:208030)
• plaque load in the hippocampus is reduced as compared to mice with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone, but still higher than wild type
• 20-30% reduction of levels of Abeta42 and Abeta40 in the hippocampus as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

homeostasis/metabolism
• plaque load in the hippocampus is reduced as compared to mice with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone, but still higher than wild type
• 20-30% reduction of levels of Abeta42 and Abeta40 in the hippocampus as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas


Mouse Genome Informatics
cx5
    Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
Tg(Thy1-MAPT*)30Schd/0

involves: C57BL/6 * C57BL/6J * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• decreased survival at 10 months of age

nervous system
• plaque load is reduced compared to mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone
• at 9 months of age compared to wild-type mice and mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone
• detected in the hippocampus, cortex, and spinal cord
• tangles in hippocampal neurons are composed of straight filaments with a wavy appearance and of occasional paired helical filaments
• density of tangles in the spinal cord increases strongly from 3 to 9 months of age
• density of tangles in the hippocampus and cortex is increased compared to mice hemizygous for Tg(Thy1-MAPT*)30Schd alone
• age of onset of tangles is earlier compared to mice hemizygous for Tg(Thy1-MAPT*)30Schd alone
• dilated dystrophic neurites at 9 months of age

behavior/neurological
• at 6 and 8 months of age compared to wild-type mice and mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone
• impairment is more severe than in mice hemizygous for Tg(Thy1-MAPT*)30Schd alone

growth/size/body
• significant and progressive reduction in body weight starting at 6 months of age

homeostasis/metabolism
• plaque load is reduced compared to mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:201809


Mouse Genome Informatics
tg6
    Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• retinal amyloid beta accumulates in the retinal pigment epithelial (RPE) layer and amyloid beta deposits are seen beneath the RPE layer

nervous system
• retinal amyloid beta accumulates in the retinal pigment epithelial (RPE) layer and amyloid beta deposits are seen beneath the RPE layer

pigmentation
• abundant intracellular amyloid beta is seen in the cytosol of RPE and with increasing intracellular accumulation of amyloid beta, tight junction integrity is attenuated and disorganized
• 12 month old mutants show hypopigmentation in the RPE layer

vision/eye
• drusen-like deposit is seen between the retinal pigment epithelium (RPE) layer and Bruch membrane in 12 month old mutants
• large vacuoles are seen in the retina of 12 month old mutants
• abundant intracellular amyloid beta is seen in the cytosol of RPE and with increasing intracellular accumulation of amyloid beta, tight junction integrity is attenuated and disorganized
• 12 month old mutants show hypopigmentation in the RPE layer
• thickened Bruch membrane is seen in the retina of 12 month old mutants

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:214858


Mouse Genome Informatics
tg7
    Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
involves: C57BL/6 * C57BL/6J * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• decreased survival at 10 months of age

nervous system

homeostasis/metabolism


Mouse Genome Informatics
tg8
    Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• by 4-5 months of age, defects in Y-maze alternation are detected in transgenic mice, indicating impaired spatial learning/memory

nervous system
• mice show Abeta42 deposits at 2 months of age; Abeta40 levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition
• amyloid deposition increases rapidly with increasing age
• plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice
• transgenic mice display neuroinflammation
• cortical layer 1 is significantly thinner than in control brains
• neurons in subiculum are very pale, or absent
• microgliosis and astrogliosis is seen in plaque-bearing regions of the brain by 2 months of age; numbers of activated astrocytes and microglia increases with age
• some neurons contain intraneuronal aggregates and display disrupted morphology
• large neurons in cortical layer 5 are reduced in number
• synapse degeneration begins at 4 months of age, compared to nontransgenic controls, as shown by reduction in levels of synaptic markers; neurodeneration marker p25 level is ~150% of control at 9 and 12 months

immune system
• transgenic mice display neuroinflammation

homeostasis/metabolism
• mice show Abeta42 deposits at 2 months of age; Abeta40 levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition
• amyloid deposition increases rapidly with increasing age
• plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:112949
Alzheimer Disease; AD 104300 J:112949


Mouse Genome Informatics
tg9
    Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
involves: 129S4/SvJae * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• impaired survival compared to wild-type mice
• survive longer than transgenic mice that are also Apoa4 null

nervous system

homeostasis/metabolism

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:169682


Mouse Genome Informatics
tg10
    Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• poor novel object recognition
• decreased % of time freezing in contextual fear conditioning test
• decreased % of time freezing in cued fear conditioning test

hematopoietic system
• increased percentage of activated microglia as compared to controls

immune system
• increased percentage of activated microglia as compared to controls

nervous system
• increased percentage of activated microglia as compared to controls
• increased plaque load and size as compared to controls
• high levels of Abeta42 and Abeta40 in the hippocampus as compared to mice that also carry Cdk5r1tm2.1Lht
• increased percentage of reactive astrocytes as compared to controls
• decreased magnitude of long term depression as compared to controls

homeostasis/metabolism
• increased plaque load and size as compared to controls
• high levels of Abeta42 and Abeta40 in the hippocampus as compared to mice that also carry Cdk5r1tm2.1Lht