Mouse Genome Informatics
cx1
    Psen1tm1Mpm/Psen1tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/?

B6.Cg-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants attend less accurately to short, spatially unpredictable stimuli when the attentional demand of the task is high and also show a general tendency to make more perseverative responses than wild-type mice
• mutants initially respond as accurately as wild-type mice, however subsequently they fail to sustain their attention over the duration of the task, indicating reduced vigilance, or ability to sustain attention over a long period of time
• treatment of mice with the cholinesterase inhibitor donepezil results in an enhanced ability to sustain attention

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:170670


Mouse Genome Informatics
cx2
    Cx3cr1tm1Litt/Cx3cr1tm1Litt
Psen1tm1Mpm/Psen1tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/0
Tg(Thy1-YFP)HJrs/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• mice do not exhibit the neuron loss or increase in microglial density and migration velocity observed in Cx3cr1tm1Litt/Cx3cr1+ Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice (J:159680)


Mouse Genome Informatics
cx3
    Cx3cr1tm1Litt/Cx3cr1+
Psen1tm1Mpm/Psen1tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/0
Tg(Thy1-YFP)HJrs/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• microglial density increases over time around lost neurons unlike in Cx3cr1tm1Litt/Cx3cr1tm1Litt Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice
• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1tm1Litt heterozygotes and homozygotes
• of YFP+ layer III neurons at 4 to 6 months

immune system
• microglial density increases over time around lost neurons unlike in Cx3cr1tm1Litt/Cx3cr1tm1Litt Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice
• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1tm1Litt heterozygotes and homozygotes

hematopoietic system
• microglial density increases over time around lost neurons unlike in Cx3cr1tm1Litt/Cx3cr1tm1Litt Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa mice
• microglia migration velocity around lost neurons is 2-fold greater than in Cx3cr1tm1Litt heterozygotes and homozygotes


Mouse Genome Informatics
cx4
    Psen1tm1Mpm/Psen1tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• in Morris water mazed, learning of task is normal but retention is impaired; 6-month old mice require 6 days of training to achieve escape latency of >20 seconds, compared to 3 days in 2 month old control mice
• at 4 and 6 months, mice show longer escape latencies in the first daily trial relative to the last trial of the previous training day indicating day-to-day retention impairment; 2-month old mice do not show this impairment in retention
• short- (1.5 hr posttraining) and long-term (24 hr posttraining) spatial recognition memory in probe trials are impaired at 6 months, whereas 4-month old mice show similar performance at 1.5 hours and impaired retention at 24 hours
• after clearance of intraneuronal Abeta using antibodies, early retention deficits are ablated, whereas long-term retention remains impaired
• at 6 months, naive and trained mice display significantly impaired long- and short-term retention for contextual fear; at 4 months, mice have normal retention for short-term (1.5 hr) contextual fear but impaired memory of contextual fear at 24 hours

nervous system
• at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons
• prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation
• treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

other phenotype
• at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons
• prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation
• treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:99604


Mouse Genome Informatics
cx5
    Psen1tm1Mpm/Psen1tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• tau pathology is detected initially by 6 months of age, and tangle pathology is advanced by 20 months
• Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months
• intraneuronal oligomers are detected at 4-6 months of age

other phenotype
• Abeta oligomers begin to accumulate between 2 and 6 months of age, with continued age-dependent increase observed between 12 and 20 months
• intraneuronal oligomers are detected at 4-6 months of age