Mouse Genome Informatics
cx1
    Pin1tm1Tuc/Pin1tm1Tuc
Tg(APPSWE)2576Kha/0

involves: 129 * 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• levels of insoluble amyloid beta, especially amyloid beta42, are increased by 46% at 6 months of age compared to single Tg(APPSWE)2576Kha hemizygous controls
• however, levels of soluble amyloid beta40 and amyloid beta42 are not affected
• amyloid beta42 predominately accumulates in multivesicular bodies of neurons
• levels of total APPs and beta-APPs are increased by about 3-fold, but levels of alpha-APPs are reduced by about 50% compared to single Tg(APPSWE)2576Kha hemizygous controls, indicating an increase in amyloidogenic versus non-amyloidogenic APP processing and thus elevation of the amyloid beta42

homeostasis/metabolism
• levels of insoluble amyloid beta, especially amyloid beta42, are increased by 46% at 6 months of age compared to single Tg(APPSWE)2576Kha hemizygous controls
• however, levels of soluble amyloid beta40 and amyloid beta42 are not affected
• amyloid beta42 predominately accumulates in multivesicular bodies of neurons
• levels of total APPs and beta-APPs are increased by about 3-fold, but levels of alpha-APPs are reduced by about 50% compared to single Tg(APPSWE)2576Kha hemizygous controls, indicating an increase in amyloidogenic versus non-amyloidogenic APP processing and thus elevation of the amyloid beta42

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:107132


Mouse Genome Informatics
cx2
    Psen1tm1Dgf/Psen1tm1Dgf
Tg(APPSWE)2576Kha/?

involves: 129 * C57BL/6 * CD-1 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• accelerated onset of amyloid deposition in a gene-dosage dependent manner
• amyloid-beta deposition was widely distributed throughout the brain and spinal cord

homeostasis/metabolism
• accelerated onset of amyloid deposition in a gene-dosage dependent manner
• amyloid-beta deposition was widely distributed throughout the brain and spinal cord

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:102425


Mouse Genome Informatics
cx3
    Nos2tm1Lau/Nos2tm1Lau
Tg(APPSWE)2576Kha/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• plaque levels elevated in the brain relative to control mice carrying the transgene only (J:112919)
• deposits are observed by 52 weeks of age (J:143551)
• double mutant exhibits increased (3172 pg/ml v. 662 pg/ml) total deposits relative to control transgenic Tg(APPSWE)2576Kha (J:143551)
• ratio of Abeta40:Abeta42 in double mutant is increased (3.8 : 1.5) relative to control transgenic Tg(APPSWE)2576Kha (J:143551)
• neuronal loss in hippocampus, subiculum and CA3 is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha
• neuronal loss in hippocampus, subiculum and CA3 is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha
• neuronal loss in subiculum is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha
• widespread cortical neuron damage

behavior/neurological
• higher level of errors in day 2 of radial arm water maze in double mutant relative to single mutants Tg(APPSWE)2576Kha or homozygous Nostm1Lau

homeostasis/metabolism
• plaque levels elevated in the brain relative to control mice carrying the transgene only (J:112919)
• deposits are observed by 52 weeks of age (J:143551)
• double mutant exhibits increased (3172 pg/ml v. 662 pg/ml) total deposits relative to control transgenic Tg(APPSWE)2576Kha (J:143551)
• ratio of Abeta40:Abeta42 in double mutant is increased (3.8 : 1.5) relative to control transgenic Tg(APPSWE)2576Kha (J:143551)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:112919


Mouse Genome Informatics
cx4
    Apoetm2(APOE*3)Mae/Apoetm2(APOE*3)Mae
Tg(APPSWE)2576Kha/?

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• increased levels of Amyloid beta 1-40 in cortical extracts at 3 months of age
• increased ratio of Amyloid beta 40:42 in cortical extracts at 3 months of age
• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age
• deposition delayed until after 12 months of age
• less plaque development than in Tg(APPSWE)2576Kha, Apoetm3(APOE*4Mae mice

homeostasis/metabolism
• increased levels of Amyloid beta 1-40 in cortical extracts at 3 months of age
• increased ratio of Amyloid beta 40:42 in cortical extracts at 3 months of age
• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age
• deposition delayed until after 12 months of age
• less plaque development than in Tg(APPSWE)2576Kha, Apoetm3(APOE*4Mae mice


Mouse Genome Informatics
cx5
    Apoetm3(APOE*4)Mae/Apoetm3(APOE*4)Mae
Tg(APPSWE)2576Kha/?

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• increased levels of Amyloid beta 1-40 in cortical extracts at 3 months of age
• increased ratio of Amyloid beta 40:42 in cortical extracts at 3 months of age
• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age
• deposition delayed until after 12 months of age
• Amyloid beta deposition starts around 12-15 months of age
• deposition is almost exclusively in cerebral blood vessels with very few parenchymal plaques at 15 months
• Amyloid beta deposition starts around 12-15 months of age
• deposition is almost exclusively in cerebral blood vessels

homeostasis/metabolism
• increased levels of Amyloid beta 1-40 in cortical extracts at 3 months of age
• increased ratio of Amyloid beta 40:42 in cortical extracts at 3 months of age
• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age
• deposition delayed until after 12 months of age
• Amyloid beta deposition starts around 12-15 months of age
• deposition is almost exclusively in cerebral blood vessels with very few parenchymal plaques at 15 months
• Amyloid beta deposition starts around 12-15 months of age
• deposition is almost exclusively in cerebral blood vessels

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:98636


Mouse Genome Informatics
cx6
    Vps35Gt(RRK261)Byg/Vps35+
Tg(APPSWE)2576Kha/0

involves: 129P2/OlaHsd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• mice exhibit normal paired-pulse facilitation and inhibitory synaptic transmission (J:178937)
• in the hippocampus and cerebral cortex
• greater accumulation than in Tg(APPSWE)2576Kha mice
• accelerated compared to in Tg(APPSWE)2576Kha mice
• field excitatory postsynaptic potential slopes in the CA1 and dentate gyrus are reduced compared to in either single heterozygotes
• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice
• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice
• in the CA1 at 2 months
• worsened at 4 months in the CA1
• however, long term potentiation in the dentate gyrus is normal
• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice
• at 4 months in the CA1

behavior/neurological
• in a Morris water maze, mice exhibit increased latencies to finding the hidden platform and in pathway length compared with either single heterozygote
• deficits increase with age

homeostasis/metabolism
• in the hippocampus and cerebral cortex
• greater accumulation than in Tg(APPSWE)2576Kha mice


Mouse Genome Informatics
cx7
    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


Mouse Genome Informatics
cx8
    Psen1tm1Dgf/Psen1+
Tg(APPSWE)2576Kha/0

involves: 129S1/Sv * 129X1/SvJ * CD-1 * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• accelerated onset of amyloid plaque deposition and increased amyloidogenic processing of APP compared to single Tg(APPSWE)2576Kha mice
• mutants exhibit enhanced reactive gliosis compared to single Tg(APPSWE)2576Kha mice

homeostasis/metabolism
• accelerated onset of amyloid plaque deposition and increased amyloidogenic processing of APP compared to single Tg(APPSWE)2576Kha mice


Mouse Genome Informatics
cx9
    Cd40lgtm1Flv/Cd40lgtm1Flv
Tg(APPSWE)2576Kha/0

involves: 129S2/SvPas * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• no detectable plaques at 12 months of age compared to minimal levels in mice carrying the transgene alone (J:80429)
• 41-51% reduction in beta-amyloid at 16 months as compared to transgene controls (J:80429)
• reduced numbers of large and medium sized plaques in the neocortex and hippocampus (J:80429)
• beta-CTF is reduced relative to alpha-CTF (J:80429)
• microgliosis and astrocytosis reduced (J:80429)

homeostasis/metabolism
• no detectable plaques at 12 months of age compared to minimal levels in mice carrying the transgene alone (J:80429)
• 41-51% reduction in beta-amyloid at 16 months as compared to transgene controls (J:80429)
• reduced numbers of large and medium sized plaques in the neocortex and hippocampus (J:80429)
• beta-CTF is reduced relative to alpha-CTF (J:80429)

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Immunodeficiency with Hyper-IgM, Type 1; HIGM1 308230 J:80429


Mouse Genome Informatics
cx10
    Ccr2tm1Ifc/Ccr2tm1Ifc
Tg(APPSWE)2576Kha/0

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
• by 130 days, 85% of mice are dead compared with 30% of mice expressing Tg(APPSWE)2576Kha, 1% of wild-type mice, and 3% of Ccr2tm1Ifc homozygotes

nervous system
• microglia accumulation is impaired compared to in mice expressing Tg(APPSWE)2576Kha
• however, microglial proliferation and responses to beta-amyloid are normal
• at P65 without classic plaques

immune system
• microglia accumulation is impaired compared to in mice expressing Tg(APPSWE)2576Kha
• however, microglial proliferation and responses to beta-amyloid are normal

cardiovascular system

hematopoietic system
• microglia accumulation is impaired compared to in mice expressing Tg(APPSWE)2576Kha
• however, microglial proliferation and responses to beta-amyloid are normal

homeostasis/metabolism
• at P65, accumulation of beta-amyloid 1-42 and 1-40 in the brain are 2.4-fold and 1.4-fold respectively compared to in mice expressing Tg(APPSWE)2576Kha
• at P65 without classic plaques


Mouse Genome Informatics
cx11
    Ccr2tm1Ifc/Ccr2+
Tg(APPSWE)2576Kha/0

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
• by 130 days, 60% of mice are dead compared with 30% of mice expressing Tg(APPSWE)2576Kha, 1% of wild-type mice, and 3% of Ccr2tm1Ifc homozygotes


Mouse Genome Informatics
cx12
    Dab1tm1Bwh/Dab1tm1Bwh
Tg(APPSWE)2576Kha/0

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
nervous system
• the loss of divisions between some folia is apparent
• the vermis to whole brain ratio is smaller than in Dab1tm1Bwh homozygotes


Mouse Genome Informatics
cx13
    Appd1FVB/NCr/Appd1FVB/NCr
Tg(APPSWE)2576Kha/0

involves: 129S6/SvEvTac * C57BL/6 * FVB/NCr * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging


Mouse Genome Informatics
cx14
    Appd2FVB/NCr/Appd2FVB/NCr
Tg(APPSWE)2576Kha/0

involves: 129S6/SvEvTac * C57BL/6 * FVB/NCr * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging


Mouse Genome Informatics
cx15
    Slc30a3tm1Rpa/Slc30a3tm1Rpa
Tg(APPSWE)2576Kha/0

involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• plaque formation and insoluble amyloid beta levels are reduced relative to hemizygous Tg(APPSWE)2576HKahs mice that carried two wild copies of Slc30a3
• no sexual difference in synaptic zinc levels, plaque formation, or insoluble amyloid beta levels
• plaques are smaller in size than in single Tg(APPSWE)2576Kha hemizygotes
• mutants exhibit an increased ratio of souluble/insoluble amyloid beta at 18 months of age compared to single Tg(APPSWE)2576Kha hemizygotes

homeostasis/metabolism
• males and females exhibit a decrease in levels of synaptic and total zinc compared to single Tg(APPSWE)2576Kha hemizygotes
• plaque formation and insoluble amyloid beta levels are reduced relative to hemizygous Tg(APPSWE)2576HKahs mice that carried two wild copies of Slc30a3
• no sexual difference in synaptic zinc levels, plaque formation, or insoluble amyloid beta levels
• plaques are smaller in size than in single Tg(APPSWE)2576Kha hemizygotes
• mutants exhibit an increased ratio of souluble/insoluble amyloid beta at 18 months of age compared to single Tg(APPSWE)2576Kha hemizygotes


Mouse Genome Informatics
cx16
    Psen1tm1Zhe/Psen1tm1Zhe
Tg(APPSWE)2576Kha/?

involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• dramatically higher plaque density in brain compared to control Tg(APPSWE)2576Kahs transgenic mice
• numerous plaques could be detected in both the cortex and hippocampus at 10 month

homeostasis/metabolism
• dramatically higher plaque density in brain compared to control Tg(APPSWE)2576Kahs transgenic mice
• numerous plaques could be detected in both the cortex and hippocampus at 10 month

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:107251


Mouse Genome Informatics
cx17
    Ldlrtm1Her/Ldlrtm1Her
Tg(APPSWE)2576Kha/0

involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• make more entries into the open arms of an elevated plus maze on day 2 of testing
• fail to show intersession habituation over 3 days of testing in an open field, unlike transgenic mice wild-type for Ldlr
• learning impairment in a Morris water maze at 10 months of age
• impairment not affected by Ldlr genotype
• at 13 months of age mice trained at 10 months of age are slower to reacquire the location of the hidden platform in a morris water maze compared to transgenic mice wild-type for Ldlr
• in a probe trial mice fail to occupy the target quadrant longer than chance indicating memory retention deficits
• relative to non-transgenic controls

homeostasis/metabolism
• hypercholesterolemia with the increase in the non-HDL fraction
• increase is mainly in the LDL fraction
• age dependent cerebral amyloidosis
• plaques first appear in the hippocampus and cortex at around 11 months
• progressive accumulation in the brain after 11 months
• cerebral amyloid beta deposition is increased compared to transgenic mice wild-type for Ldlr

nervous system
• cerebral amyloid beta deposition is increased compared to transgenic mice wild-type for Ldlr

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:114480


Mouse Genome Informatics
cx18
    Pld2tm1.1Gdp/Pld2tm1.1Gdp
Tg(APPSWE)2576Kha/0

involves: 129X1/SvJ * 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
• mice exhibit normal spatial working memory unlike Tg(APPSWE)2576Kha mice (J:166741)
• compared to Tg(APPSWE)2576Kha mice

homeostasis/metabolism
• mice exhibit altered levels of specific phosphatidic acids compared to in wild-type mice

nervous system
• mice exhibit synaptic protection compared to in Tg(APPSWE)2576Kha mice


Mouse Genome Informatics
cx19
    Pld2tm1.1Gdp/Pld2+
Tg(APPSWE)2576Kha/0

involves: 129X1/SvJ * 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
• mice exhibit normal spatial working memory unlike Tg(APPSWE)2576Kha mice (J:166741)
• compared to Tg(APPSWE)2576Kha mice


Mouse Genome Informatics
cx20
    Hspa4tm1.1Miv/Hspa4tm1.1Miv
Tg(APPSWE)2576Kha/0

involves: BALB/cJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• many mice die before 7 months of age

nervous system
• at 6 months, mice develop neurofibril tangles unlike Tg(APPSWE)2576Kha mice
• at 7 months, mice develop senility plaques unlike Tg(APPSWE)2576Kha mice
• neuron degeneration is more severe than in Tg(APPSWE)2576Kha mice


Mouse Genome Informatics
cx21
    Tg(APPSWE)2576Kha/0
Tg(Prnp-ITM2B/APP695*42)A12Emcg/0

involves: C3H * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• augmentation of Abeta deposits throughout cortex, hippocampus, and cerebellum is observed in double transgenic mice at 14.5 month-old mice, relative to single transgenics
• mice show enhanced senile plaque pathology in the forebrain at 14.5 months
• mice show elevated insoluble Abeta levels in the hindbrain at 14.5 months

homeostasis/metabolism
• formic acid extractable Abeta40 and Abeta42 levels are dramatically elevated at 14.5 months in hindbrain compared Tg(APPSWE)2576Kahs single transgenic mice; levels of Abeta42 are slightly higher than those observed in forebrains of Tg(Prnp-ITM2B/APP695*42)A12Emcg mice at 14.5 months, while Abeta40 levels are significantly higher than in either single transgenic mouse
• augmentation of Abeta deposits throughout cortex, hippocampus, and cerebellum is observed in double transgenic mice at 14.5 month-old mice, relative to single transgenics


Mouse Genome Informatics
cx22
    Psen1tm1.1Tcs/Psen1tm1.1Tcs
Tg(APPSWE)2576Kha/0

involves: C57BL/6 * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 3 to 4 months in a Y-maze test

nervous system
• beginning at 6 months, earlier than in Tg(APPSWE)2576Kha mice at 12 months
• fewer plaques than in Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSWE)2576Kha mice
• at 9 months

homeostasis/metabolism
• beginning at 6 months, earlier than in Tg(APPSWE)2576Kha mice at 12 months
• fewer plaques than in Psen1tm1Mpm/Psen1tm1Mpm Tg(APPSWE)2576Kha mice


Mouse Genome Informatics
cx23
    Tg(APPSWE)2576Kha/0
Tg(PDGFB-PSEN1M146L)2Jhd/0

involves: C57BL/6 * DBA/2 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at <3 months of age, mice show amyloid beta deposits in frontal cortex; with age, deposits spread throughout cortex, and to the hippocampus, thalamus and dentate gyrus
• by 1 year of age, deposits are widely observed, with no apparent increase in total amount of amyloid deposited after this age
• some fibrillar amyloid beta deposits are detected in the frontal cortex of youngest mice, with absence of deposits in more caudal regions; number of fibrillar deposits increases up to 1 year of age, with area covered by fibrillar deposits increasing up to 2 years of age
• at 1 year, area covered by fibrillar deposits is ~50% of total amyloid beta, but comprises majority of total covered area by 2.5 years of age
• ins some areas of cortex in older animals,astrocytes appear dystrophic and are no longer closely associated with plaques, although nearby plaques are associated with activated glial cells
• activated microglia accumulate around amyloid beta deposits from ~ 3 months; number of glia increases with age and amyloid accumulation
• activated astrocytes accumulate around amyloid deposits in frontal cortex of 3 month old mice

homeostasis/metabolism
• at <3 months of age, mice show amyloid beta deposits in frontal cortex; with age, deposits spread throughout cortex, and to the hippocampus, thalamus and dentate gyrus
• by 1 year of age, deposits are widely observed, with no apparent increase in total amount of amyloid deposited after this age
• some fibrillar amyloid beta deposits are detected in the frontal cortex of youngest mice, with absence of deposits in more caudal regions; number of fibrillar deposits increases up to 1 year of age, with area covered by fibrillar deposits increasing up to 2 years of age
• at 1 year, area covered by fibrillar deposits is ~50% of total amyloid beta, but comprises majority of total covered area by 2.5 years of age


Mouse Genome Informatics
cx24
    Tg(APPSWE)2576Kha/?
Tg(PDGFB-PSEN1M146L)2Jhd/?

involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• treatment with antibody to CD40L results in more diffuse beta-amyloid plaques
• equal levels of alpha- and beta-CTF
• antibody to CD40L produces increased levels of circulating beta amyloid
• microgliosis and astrocytosis reduced in the hippocampus, and entorhinal cortex
• astrocytosis also reduced in the cingulated cortex

homeostasis/metabolism
• treatment with antibody to CD40L results in more diffuse beta-amyloid plaques
• equal levels of alpha- and beta-CTF
• antibody to CD40L produces increased levels of circulating beta amyloid


Mouse Genome Informatics
cx25
    Tg(APPSWE)2576Kha/0
Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0

involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• progressive hindlimb weakness is observed

nervous system
• mice have amyloid plaques similar in number and distribution to Tg(APPSWE)2576Kha mice; plaques are detected as early as 6 months, but do become numerous only in older mice (8.5 to 15 months) in the olfactory cortex, cingulated gyrus, amygdala, entorhinal cortex, and hippocampus
• deposits contain both Abeta1-40 and Abeta1-42 peptides
• by 3 months of age, neurofibrillary tangles (NFTs) composed of straight fibers sometimes forming complex structures are detected in the spinal cords and pons of transgenic animals, and become more numerous with age
• older females 9-11 months of age display marked increases in NFTs in limbic areas, such as the olfactory cortex, entorhinal cortex, and amygdala; density of NFTs in females is >7-fold higher than in Tg(Prnp-MAPT*P301L)JNPL3 littermates
• norm male animals do not develop enhanced NFT pathology in limbic regions
• NFTs are also found in subiculum, hippocampus and sometimes in the isocortex, whereas NFTs are never or rarely observed in these brain regions of Tg(Prnp-MAPT*P301L)JNPL3 animals
• number and distribution of pretangles is increased in 9-11 month-old mice in limbic areas and cerebral cortex
• levels of soluble endogenous and transgenic Tau protein are similar to Tg(Prnp-MAPT*P301L)JNPL3Hlmc transgenic mice; 64-kd insoluble tau species in increased in cortex/limbic regions of females 9-11 months compared to Tg(Prnp-MAPT*P301L)JNPL3Hlmc mice
• as severe as astrocytosis in ventral diencepalon, hindbrain, and spinal cord
• increase observed in limbic areas with the most NFTs
• Tau filaments occupy large proportion of cell volume, displacing nucleus and cytoplasmic organelles and compressing the Golgi apparatus
• dystrophic neurites reactive for APP epitopes are associated with amyloid plaques
• neurofibrillary degeneration resulting from accumulation of NFTs is observed as early as 6 months
• granulovacuolar degeneration is seen in neurons of amygdala, entorhinal cortex, and subiculum of females, characterized by optically clear vacuoles with dense cores

vision/eye
• increased eye irritation

homeostasis/metabolism
• mice have amyloid plaques similar in number and distribution to Tg(APPSWE)2576Kha mice; plaques are detected as early as 6 months, but do become numerous only in older mice (8.5 to 15 months) in the olfactory cortex, cingulated gyrus, amygdala, entorhinal cortex, and hippocampus
• deposits contain both Abeta1-40 and Abeta1-42 peptides

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:100965


Mouse Genome Informatics
cx26
    Tg(APPSWE)2576Kha/0
Tg(PDGFB-PSEN1M146L)2Jhd/0

involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• kidney glomeruli are dilated probably due to obstruction from the amyloid in the lumen or walls of medullary tubules especially in the papilla

homeostasis/metabolism
• some mutants older than 18 months exhibit amyloid deposits in the spleen and kidneys, and occasionally in the liver, ovary and/or heart
• amyloid is deposited concentrically in the perifollicular sheath, partly or completely encircling the follicles in the spleen
• in the liver, amyloid deposit is in the walls of sinusoids or central veins
• in the kidney, amyloid deposits are seen in the glomeruli
• amyloid deposits in the heart are not composed of amyloid-beta peptide, but rather amyloid A

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:174270


Mouse Genome Informatics
cx27
    Tg(APPSWE)2576Kha/0
Tg(PSEN1)5Dbo/0

involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• dense amyloid beta plaques in the cortex and hippocampus, but not in the adrenal medulla
• amperometric recordings from chromaffin cells stimulated with a 10 second 70 mM potassium pulse indicate that the quantity of catecholamines released during the initiation of the fusion pore is 50% smaller in mutants than in controls
• chromaffin cells exhibit smaller quantal size and faster kinetics of single exocytotic events (45% lower spike half-width, 60% smaller quantal size, 50% lower decay time) and spike feet show 60% smaller quantal size
• mutants, however, exhibit normal innervation by splanchnic cholinergic nerve terminals of chromaffin cells

homeostasis/metabolism
• chromaffin cells release 50% less catecholamine (mean quantal content released per vesicle is halved) in response to a 10 second 70 mM potassium pulse
• dense amyloid beta plaques in the cortex and hippocampus, but not in the adrenal medulla

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:191088


Mouse Genome Informatics
tg28
    Tg(APPSWE)2576Kha/Tg(APPSWE)2576Kha
involves: 129S7/SvEvBrd * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants die prematurely; time not specified


Mouse Genome Informatics
tg29
    Tg(APPSWE)2576Kha/0
FVB.Cg-Tg(APPSWE)2576Kha
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: ~44% of mice die before 150 days of age

behavior/neurological
• Background Sensitivity: 25% of mice display neophobia compared to none on mixed genetic background


Mouse Genome Informatics
tg30
    Tg(APPSWE)2576Kha/0
involves: 129S7/SvEvBrd * 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
• 12 month old mice exhibit normal motor coordination on the rotarod (J:180385)
• spend more time in the open arms of an elevated plus maze
• mutants exhibit impaired long-trace interval eyeblink conditioning at 6 months of age
• however, mutants do not exhibit impaired delay eyeblink conditioning even at 12 months of age, although it is slightly but insignificantly decreased
• impaired spatial learning in a morris water maze
• in a probe trial mice fail to occupy the target quadrant longer than chance indicating memory retention deficits

homeostasis/metabolism
• females exhibit an increase in levels of synaptic zinc with aging
• increase in insoluble amyloid beta and plaques with aging; greater increase in plaques in females than males (J:76863)

nervous system
• increase in insoluble amyloid beta and plaques with aging; greater increase in plaques in females than males (J:76863)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:114480 , J:180385


Mouse Genome Informatics
tg31
    Tg(APPSWE)2576Kha/0
involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice display amyloid plaques as early as 6 months, but do become numerous only in older mice (8.5 to 15 months)
• deposits contain both Abeta1-40 and Abeta1-42 peptides

renal/urinary system
• kidney glomeruli are dilated probably due to obstruction from the amyloid in the lumen or walls of medullary tubules especially in the papilla

homeostasis/metabolism
• some mutants older than 18 months exhibit amyloid deposits in the spleen, kidneys, liver, ovary and/or heart
• amyloid is deposited concentrically in the perifollicular sheath, partly or completely encircling the follicles in the spleen
• amyloid replaces most of the splenic red pulp
• in the liver, amyloid deposit is in the walls of sinusoids or central veins
• in the kidney, amyloid deposits are seen in the glomeruli
• amyloid deposits in the heart are not composed of amyloid-beta peptide, but rather amyloid A
• mice display amyloid plaques as early as 6 months, but do become numerous only in older mice (8.5 to 15 months)
• deposits contain both Abeta1-40 and Abeta1-42 peptides

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:174270


Mouse Genome Informatics
tg32
    Tg(APPSWE)2576Kha/0
involves: C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at 24 months
• only occur in forebrain after 6 months of age, and no cerebellar deposits are routinely observed (J:101023)
• at 2 years (J:121703)
• at 24 months, mice develop amyloid plaques in the cerebral cortex and hippocampus unlike wild-type mice (J:159623)
• at 24 months

cardiovascular system
• after myocardin gene transfer to neocortical pial vessels in 16-month old mice, mice show significant reduction in cerebral blood flow response to whisker stimulation

hematopoietic system
• at 24 months

immune system
• at 24 months

homeostasis/metabolism
• formic acid extractable Abeta40 and Abeta42 levels are dramatically elevated at 14.5 months compared to Tg(Prnp-ITM2B/APP695*42)A12Emcg mice
• only occur in forebrain after 6 months of age, and no cerebellar deposits are routinely observed (J:101023)
• at 2 years (J:121703)
• at 24 months, mice develop amyloid plaques in the cerebral cortex and hippocampus unlike wild-type mice (J:159623)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:119251


Mouse Genome Informatics
tg33
    Tg(APPSWE)2576Kha/0
involves: C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• transmission of transgene decreases from expected 50% with each backcross generation, suggesting that there is pre-weaning or in utero lethality of transgenic mice; N2 generation mice crossed to (C57BL x SJL)F1 mice show restoration of expected 50% transmission and decreased early mortality (16% vs 36% in N2 generation)
• after 1 backcross to C57BL/6 (or N1 generation), 1/3 mice die by <150 days of age; N2 generation mice show 36% lethality with median age at death of ~87 days, while in the N3 generation, 50% mortality is seen at median age of 65 days and in the N4 generation, 100% of mice die with median age of 65 days

behavior/neurological
N
• Background Sensitivity: mice do not show obvious behavioral abnormalities (J:43446)