Mouse Genome Informatics
cx1
    Apoetm1Unc/Apoetm2(APOE_i3)Yhg
Tg(PDGFB-APPSwInd)20Lms/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• aged mice exhibit reduced amyloid plaques compared to Apoetm2(APOE_i3)Yhg/Apoetm2(APOE_i3)Yhg Tg(PDGFB-APPSwInd)20Lms mice

other phenotype
• aged mice exhibit reduced amyloid plaques compared to Apoetm2(APOE_i3)Yhg/Apoetm2(APOE_i3)Yhg Tg(PDGFB-APPSwInd)20Lms mice


Mouse Genome Informatics
cx2
    Apoetm1Unc/Apoetm3(APOE_i4)Yhg
Tg(PDGFB-APPSwInd)20Lms/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• aged mice exhibit reduced amyloid plaques compared to Apoetm3(APOE_i4)Yhg/Apoetm3(APOE_i4)Yhg Tg(PDGFB-APPSwInd)20Lms mice

other phenotype
• aged mice exhibit reduced amyloid plaques compared to Apoetm3(APOE_i4)Yhg/Apoetm3(APOE_i4)Yhg Tg(PDGFB-APPSwInd)20Lms mice


Mouse Genome Informatics
cx3
    C3tm1Crr/C3tm1Crr
Tg(PDGFB-APPSwInd)20Lms/?

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• neuron loss in the CA3 region at 17 days relative to controls
• plaque levels are doubled in the hippocampus and mid frontal cortex relative to controls at 17 months of age but normal at 12 months
• plasma amyloid levels are increased 51% at 17 months

other phenotype
• plaque levels are doubled in the hippocampus and mid frontal cortex relative to controls at 17 months of age but normal at 12 months
• plasma amyloid levels are increased 51% at 17 months

immune system

hematopoietic system


Mouse Genome Informatics
cx4
    Pla2g4atm1Jvb/Pla2g4a+
Tg(PDGFB-APPSwInd)20Lms/0

involves: 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice do not exhibit premature death as do Tg(PDGFB-APPSwInd)20Lms mice (J:141084)

behavior/neurological
N
• mice do not exhibit the hyperactivity observed in Tg(PDGFB-APPSwInd)20Lms mice (J:141084)
• mice exhibit disinhibition-like behaviors in an elevated plus maze compared with wild-type mice that are not as severe as in Tg(PDGFB-APPSwInd)20Lms mice
• mice exhibit a complete or partial recovery of the learning deficits observed in Tg(PDGFB-APPSwInd)20Lms mice with improved target crossing in a Morris water maze


Mouse Genome Informatics
cx5
    Pla2g4atm1Jvb/Pla2g4atm1Jvb
Tg(PDGFB-APPSwInd)20Lms/0

involves: 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice do not exhibit premature death as do Tg(PDGFB-APPSwInd)20Lms mice (J:141084)

behavior/neurological
N
• mice do not exhibit the hyperactivity observed in Tg(PDGFB-APPSwInd)20Lms mice (J:141084)
• mice exhibit disinhibition-like behaviors in an elevated plus maze compared with wild-type mice that are not as severe as in Tg(PDGFB-APPSwInd)20Lms mice
• mice exhibit a complete or partial recovery of the learning deficits observed in Tg(PDGFB-APPSwInd)20Lms mice with improved target crossing in a Morris water maze


Mouse Genome Informatics
cx6
    Mapttm1Hnd/Mapttm1Hnd
Tg(PDGFB-APPSwInd)20Lms/0

involves: 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice show normal spatial learning and object-recongition memory, at levels similar to non-transgenic controls (J:121330)
• mice show no signs of hyperactivity (J:121330)
• seizures are less severe and occur at longer latencies compared to transgenic mice with wild-type Mapt

nervous system
• seizures are less severe and occur at longer latencies compared to transgenic mice with wild-type Mapt
• mice show neuritic dystrophy around amyloid plaques
• aberrant sprouting of hippocampal axons is observed in transgenic mice
• at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous or wild-type for Mapt

other phenotype
• at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous or wild-type for Mapt

cellular
• aberrant sprouting of hippocampal axons is observed in transgenic mice


Mouse Genome Informatics
cx7
    Mapttm1Hnd/Mapt+
Tg(PDGFB-APPSwInd)20Lms/0

involves: 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice show no signs of hyperactivity (J:121330)
• seizures are less severe and occur at longer latencies compared to transgenic mice with wild-type Mapt
• in the hidden platform version of the Morris water maze, non-trangenic controls, regardless of Mapt genotype learn the task over 3 days, whereas transgenic mice heterozygous for Mapttm1Hnd show show impaired learning compared to controls but less impairment than transgenic mice with normal Mapt expression
• in probe trials where the platform is removed, mice show delayed learning, compared to non transgenic controls or transgenic mice with wild-type Mapt, with more target than non-target crossings after 5 days of training

nervous system
• seizures are less severe and occur at longer latencies compared to transgenic mice with wild-type Mapt
• mice show neuritic dystrophy around amyloid plaques
• aberrant sprouting of hippocampal axons is observed in transgenic mice
• at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics null or wild-type for Mapt

other phenotype
• at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics null or wild-type for Mapt

cellular
• aberrant sprouting of hippocampal axons is observed in transgenic mice


Mouse Genome Informatics
cx8
    Tg(Gfap-TGFB1)64Lms/0
Tg(PDGFB-APPSwInd)20Lms/0

involves: BALB/c * C57BL/6 * DBA/2 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 6-8 month old mutants show increased latencies to locate the hidden platform in the Morris water maze indicating a learning deficit
• 12- and 18-month old mutants show impaired probe trial performance, indicating a memory impairment

cardiovascular system
• mutants exhibit significant collagen accumulation in penetrating intraparenchymal microvessels
• mutants exhibit significant collagen accumulation in penetrating intraparenchymal microvessels and in the surface pial membrane, resulting in increased thickness
• middle cerebral arteries show a 50% loss of ability to dilate in response to acetylcholine and calcitonin gene-related peptide compared to wild-type vessels
• arterial dysfunction is not due to oxidative stress
• by 18 months of age, mutants exhibit impaired maximal diameter decrease during NOS inhibition with N-nitro-L-arginine
• however, contractile response of arteries to endothelin-1 is normal

muscle
• middle cerebral arteries show a 50% loss of ability to dilate in response to acetylcholine and calcitonin gene-related peptide compared to wild-type vessels
• arterial dysfunction is not due to oxidative stress
• by 18 months of age, mutants exhibit impaired maximal diameter decrease during NOS inhibition with N-nitro-L-arginine
• however, contractile response of arteries to endothelin-1 is normal

nervous system
• mutants exhibit significant collagen accumulation in penetrating intraparenchymal microvessels and in the surface pial membrane, resulting in increased thickness
• 18 month old mutants exhibit widespread cerebral amyloid angiopathy in pial, intracortical, and hippocampal brain vessels
• mutants exhibit activated GFAP-positive astrocytes in the cortex; activated astrocytes are distributed in clusters as well as diffusely throughout the cortex
• mutants exhibit significant collagen accumulation in the surface pial membrane, resulting in increased thickness
• about 22-23% reduction in the number of cortical cholinergic fibers in adults and aged-mutants
• mutants exhibit age-dependent amyloid beta plaque deposition in the cortex and hippocampus; 18 month old mutants exhibit parenchymal amyloid beta senile plaques
• mutants exhibit increased levels of soluble and insoluble amyloid beta(1-40) and amyloid beta(1-42) between 6-8 and 12 months of age and further increases in amyloid beta(1-40) at 18 months of age, in the cortex
• glucose uptake is impaired in activated somatosensory cortex of aged mutants after whisker stimulation
• gradual loss of the neuronally-driven hemodynamic response to sensory whisker stimulation

other phenotype
• 18 month old mutants exhibit widespread cerebral amyloid angiopathy in pial, intracortical, and hippocampal brain vessels
• mutants exhibit age-dependent amyloid beta plaque deposition in the cortex and hippocampus; 18 month old mutants exhibit parenchymal amyloid beta senile plaques
• mutants exhibit increased levels of soluble and insoluble amyloid beta(1-40) and amyloid beta(1-42) between 6-8 and 12 months of age and further increases in amyloid beta(1-40) at 18 months of age, in the cortex

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:167619


Mouse Genome Informatics
cx9
    Tg(Camk2a-IDE)1Selk/0
Tg(PDGFB-APPSwInd)20Lms/0

involves: C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• attenuated premature death at 6 months relative to Tg(PDGFB-APPSwInd)20Lms single transgenic littermates

nervous system
• microgliosis is reduced
• decreased relative to Tg(PDGFB-APPSwInd)20Lms single transgenic littermates
• number of dystrophic neurites is reduced relative to Tg(PDGFB-APPSwInd)20Lms single transgenic mice
• at 6-10 months, soluble and insoluble Abeta-40 and -42 peptide levels are reduced by ~50% relative to Tg(PDGFB-APPSwInd)20Lms single transgenic mice; amyloid plaque burden is reduced by ~50%

other phenotype
• at 6-10 months, soluble and insoluble Abeta-40 and -42 peptide levels are reduced by ~50% relative to Tg(PDGFB-APPSwInd)20Lms single transgenic mice; amyloid plaque burden is reduced by ~50%


Mouse Genome Informatics
cx10
    Tg(Camk2a-MME)3Selk/0
Tg(PDGFB-APPSwInd)20Lms/0

involves: C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• attenuated premature death at 6 months relative to Tg(PDGFB-APPSwInd)20Lms single transgenic littermates

nervous system
• microgliosis is reduced
• decreased relative to Tg(PDGFB-APPSwInd)20Lms single transgenic littermates
• number of dystrophic neurites is reduced relative to Tg(PDGFB-APPSwInd)20Lms single transgenic mice
• at 6-10 months, soluble and insoluble Abeta-40 and -42 peptide levels are reduced by ~90% relative to Tg(PDGFB-APPSwInd)20Lms single transgenic mice; amyloid plaques are almost absent

other phenotype
• at 6-10 months, soluble and insoluble Abeta-40 and -42 peptide levels are reduced by ~90% relative to Tg(PDGFB-APPSwInd)20Lms single transgenic mice; amyloid plaques are almost absent


Mouse Genome Informatics
tg11
    Tg(PDGFB-APPSwInd)20Lms/0
B6.Cg-Tg(PDGFB-APPSwInd)20Lms
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at 6 months and 12 to 16 months of age, 30% fewer pyramidal cells in the entorhinal cortex express Reelin than in wild-type mice
• however, no neuron loss is observed


Mouse Genome Informatics
tg12
    Tg(PDGFB-APPSwInd)20Lms/0
B6.D2-Tg(PDGFB-APPSwInd)20Lms
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• dystrophic neurites are associated with plaques
• mice develop amyloid peptide deposits by 5-7 months of age

other phenotype
• mice develop amyloid peptide deposits by 5-7 months of age


Mouse Genome Informatics
tg13
    Tg(PDGFB-APPSwInd)20Lms/0
involves: C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• high rate of premature (6 months or earlier) death (J:87150)
• mice show premature death of unclear etiology with >15% mortality exhibited by 6 months, compared to all other genotypes (J:121330)

behavior/neurological
• mice are abnormally sensitive to pentylenetetrazole (PTZ)-induced seizures with 20% suffering fatal status epilepticus at a PTZ dose not lethal in non-transgenic controls
• mice exhibit disinhibition-like behaviors in an elevated plus maze compared with wild-type mice
• at 4-7 months of age, mice transgenic mice with wild-type Mapt expression take longer to locate the platform in the cued version of the Morris water maze test compared to transgenic mice heterozygous or homozygous for Mapt deletion
• in the hidden platform version of the Morris water maze, non-trangenic controls, regardless of Mapt genotype learn the task over 3 days, whereas transgenic mice with wild-type expression of Mapt show no evidence of learning (J:121330)
• in probe trials where the platform is removed, mice show no learning, displaying no significantly elevated crossings of the target quadrant after 5 days of training (J:121330)
• in a Morris water maze, mice fail to favor the target platform location unlike wild-type mice (J:141084)
• mice show hyperactivity in the Y-maze, a new cage, and elevated-plus maze compared to other transgenic mice or non-transgenic controls; this persists in mice 12-16 months of age (J:121330)

nervous system
• mice are abnormally sensitive to pentylenetetrazole (PTZ)-induced seizures with 20% suffering fatal status epilepticus at a PTZ dose not lethal in non-transgenic controls
• mice show neuritic dystrophy around amyloid plaques
• aberrant sprouting of hippocampal axons is observed in transgenic mice
• diffuse immunoreactive amyloid deposits detected in dentate gyrus and neocortex of mice aged 5 to 7 months old (J:62290)
• all mice exhibit plaques by age 8 to 10 months (J:62290)
• soluble and insoluble Abeta-40 and -42 peptide deposits at 6-10 months (J:87150)
• at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous null for Mapt (J:121330)
• neurodegeneration is indicated by an age dependent decrease in density of synaptophysin-immunoreactive presynaptic terminals

other phenotype
• diffuse immunoreactive amyloid deposits detected in dentate gyrus and neocortex of mice aged 5 to 7 months old (J:62290)
• all mice exhibit plaques by age 8 to 10 months (J:62290)
• soluble and insoluble Abeta-40 and -42 peptide deposits at 6-10 months (J:87150)
• at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous null for Mapt (J:121330)

cellular
• aberrant sprouting of hippocampal axons is observed in transgenic mice

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:62290