Mouse Genome Informatics
hm1
    Psen1tm1Mpm/Psen1tm1Mpm
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
• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type
• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction
• homozygotes are hypersensitive to seizure-induced synaptic degeneration and necrotic neuronal death in the hippocampus

behavior/neurological
N
• homozygotes do not exhibit a deficit in contextual fear learning at 3 months of age (J:91277)
• homozygous mice do not differ in performance in Morris water maze or in contextual fear conditioning (J:99604)

homeostasis/metabolism
• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type
• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

cellular
• kainate-induced degeneration and death of CA3, CA1, and hilar neurons is accelerated and increased in mutants compared to wild-type
• cultured hippocampal neurons show increased susceptibility to death induced by glutamate, due to impaired calcium homeostasis, increased oxidative stress, and mitochondrial dysfunction

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:51950
Alzheimer Disease; AD 104300 J:51950


Mouse Genome Informatics
ht2
    Psen1tm1Mpm/Psen1tm1Shn
involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

limbs/digits/tail
• limb ateliosis
• stubby

cardiovascular system
• in the central nervous system

growth/size


Mouse Genome Informatics
ht3
    Psen1tm1Mpm/Psen1tm1Pcw
involves: 129S1/Sv * 129S7/SvEvBrd * 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
• exhibit impaired hippocampus-dependent contextual fear learning at 3 months of age, showing reduced freezing behavior
• however, show normal cued fear learning, anxiety, motor coordination and shock threshold

nervous system
• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

cellular
• exhibit a 35% decrease in the number of newborn cells in the dentate gyrus of 3-month old mutants, indicating impaired adult neurogenesis

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:91277
Alzheimer Disease; AD 104300 J:91277


Mouse Genome Informatics
cx4
    Apptm1Ck/Apptm1Ck
Psen1tm1Mpm/Psen1tm1Mpm
Tg(MAPT)8cPdav/0

B6.Cg-Psen1tm1Mpm Apptm1Ck Tg(MAPT)8cPdav
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• however, mice show normal nociception in the hot plate assay
• in the elevated plus maze, 4 month old mice spend less time on the open arm, indicating increased anxiety
• mice show slightly higher pre-shock freezing frequency and increased contextual freezing frequency at 4 and 12 months of age, indicating exaggerated fear response
• mice show increased contextual freezing frequency at 4 and 12 months of age
• however, cued freezing frequency is unaffected and mice do not exhibit spatial memory deficits in the Morris water maze
• in the open field, the total travel distance is reduced at 12, but not 4, months of age, indicating age-dependent reduced activity

homeostasis/metabolism
• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age

nervous system
• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age
• increase in phosphorylated tau in the cortex and hippocampus

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:209782


Mouse Genome Informatics
cx5
    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
cx6
    Apptm1Ck/Apptm1Ck
Psen1tm1Mpm/Psen1tm1Mpm

involves: 129 * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit decreased amyloid load compared with Apptm3.1Zhe Psen1tm1Mpm double homozygotes
• corticotropin releasing factor levels are increased in the lateral dorsal bed nucleus of the stria terminalis and the paraventricular nucleus

homeostasis/metabolism
• mice exhibit an increase in resting levels of circulating corticosterone
• mice exhibit decreased amyloid load compared with Apptm3.1Zhe Psen1tm1Mpm double homozygotes

behavior/neurological
• in the elevated plus maze, mice spend more time in the closed arms and less time in the open arms and make fewer entries into the open arms and navigate less distance on the open arms, indicating increased levels of anxiety
• in the light-dark box test, mice spend more time in the closed portion of the box and less time in the open side, make fewer entries to the light side of the box, and spend on average more time on each visit to the dark side, suggesting an increase in hiding behavior and reduction in exploring
• mice show increased freezing in the context in which they received the shock compared to wild-type mice but show similar levels of freezing as wild-type mice in cued fear (in response to sound)
• during the cued trial, mice show increased baseline freezing levels in the 3 minutes before presentation of sound, however increased baseline freezing is not seen before mice are shocked
• mice show increased freezing in the context in which they received the shock compared to wild-type mice but show similar levels of freezing as wild-type mice in cued fear (in response to sound), indicating increased contextual fear
• however, hot plate assay shows normal nociception
• in the alternation T-maze test, mice show decreased alternation, indicating reduced working memory

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:191170


Mouse Genome Informatics
cx7
    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
cx8
    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
cx9
    Apptm3.1Zhe/Apptm3.1Zhe
Psen1tm1Mpm/Psen1tm1Mpm

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Amyloid beta deposits in Apptm3.1Zhe/Apptm3.1Zhe Psen1tm1Mpm/Psen1tm1Mpm mice

nervous system
• mice exhibit increased amyloid load compared with Apptm1Ck Psen1tm1Mpm double homozygotes

homeostasis/metabolism
• mice exhibit increased amyloid load compared with Apptm1Ck Psen1tm1Mpm double homozygotes


Mouse Genome Informatics
cx10
    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

homeostasis/metabolism
• 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
cx11
    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
• 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
• tau pathology is detected initially by 6 months of age, and tangle pathology is advanced by 20 months

homeostasis/metabolism
• 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


Mouse Genome Informatics
cx12
    Psen1tm1Mpm/Psen1tm1Mpm
Tg(APPSWE)2576Kha/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice accumulate more plaques than in Psen1tm1.1Tcs/Psen1tm1.1Tcs Tg(APPSWE)2576Kha mice

homeostasis/metabolism
• mice accumulate more plaques than in Psen1tm1.1Tcs/Psen1tm1.1Tcs Tg(APPSWE)2576Kha mice