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)

other phenotype
• 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

other phenotype
• 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
• 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
• accelerated deposition compared to transgenic mice wild-type for Apoa4

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

other phenotype
• 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
tg4
    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
• 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
• 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
• 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

other phenotype
• 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
tg5
    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

other phenotype

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