All Phenotypes Tg(APPSWE)2576Kha MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Tg(APPSWE)2576Kha
transgene insertion 2576, Karen Hsiao Ashe
MGI:2385631

Summary

36 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Pin1^tm1Tuc/Pin1^tm1Tuc Tg(APPSWE)2576Kha/0	involves: 129 * 129P2/OlaHsd * C57BL/6 * SJL	MGI:5433613
cx2	Psen1^tm1Dgf/Psen1^tm1Dgf Tg(APPSWE)2576Kha/?	involves: 129 * C57BL/6 * CD-1 * SJL	MGI:3611211
cx3	Apoe^{tm1(APOE_i4)Sfu}/Apoe^{tm1(APOE_i4)Sfu} Tg(APPSWE)2576Kha/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * SJL	MGI:6450215
cx4	Vps35^{Gt(RRK261)Byg}/Vps35⁺ Tg(APPSWE)2576Kha/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5306777
cx5	Nos2^tm1Lau/Nos2^tm1Lau Tg(APPSWE)2576Kha/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:3769910
cx6	Apoe^{tm3(APOE4)Mae}/Apoe^{tm3(APOE4)Mae} Tg(APPSWE)2576Kha/?	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4355229
cx7	Apoe^{tm2(APOE3)Mae}/Apoe^{tm2(APOE3)Mae} Tg(APPSWE)2576Kha/?	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4355224
cx8	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSWE)2576Kha/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5292247
cx9	Psen1^tm1Dgf/Psen1⁺ Tg(APPSWE)2576Kha/0	involves: 129S1/Sv * 129X1/SvJ * CD-1 * C57BL/6 * SJL	MGI:2652383
cx10	Cd40lg^tm1Flv/Cd40lg^tm1Flv Tg(APPSWE)2576Kha/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:2653196
cx11	Ccr2^tm1Ifc/Ccr2^tm1Ifc Tg(APPSWE)2576Kha/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:4831169
cx12	Ccr2^tm1Ifc/Ccr2⁺ Tg(APPSWE)2576Kha/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:4831171
cx13	Dab1^tm1Bwh/Dab1^tm1Bwh Tg(APPSWE)2576Kha/0	involves: 129S4/SvJaeSor * C57BL/6 * SJL	MGI:3810279
cx14	Appd1^FVB/NCr/Appd1^FVB/NCr Tg(APPSWE)2576Kha/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/NCr * SJL	MGI:3663101
cx15	Appd2^FVB/NCr/Appd2^FVB/NCr Tg(APPSWE)2576Kha/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/NCr * SJL	MGI:3663102
cx16	Ldlr^tm1Her/Ldlr^tm1Her Tg(APPSWE)2576Kha/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:4367205
cx17	Slc30a3^tm1Rpa/Slc30a3^tm1Rpa Tg(APPSWE)2576Kha/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3029279
cx18	Psen1^tm1Zhe/Psen1^tm1Zhe Tg(APPSWE)2576Kha/?	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3624416
cx19	Pld2^tm1.1Gdp/Pld2⁺ Tg(APPSWE)2576Kha/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:4880015
cx20	Pld2^tm1.1Gdp/Pld2^tm1.1Gdp Tg(APPSWE)2576Kha/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:4880014
cx21	Hspa4^tm1.1Miv/Hspa4^tm1.1Miv Tg(APPSWE)2576Kha/0	involves: BALB/cJ * C57BL/6 * SJL	MGI:4836978
cx22	Tg(APPSWE)2576Kha/0 Tg(Prnp-ITM2B/APP695*42)A12Emcg/0	involves: C3H * C57BL/6 * SJL	MGI:3710765
cx23	Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:5292246
cx24	Apoe^{tm3(APOE_i3)Sfu}/Apoe^{tm3(APOE_i3)Sfu} Tg(APPSWE)2576Kha/0	involves: C57BL/6 * C57BL/6N * SJL	MGI:6450214
cx25	Tg(APPSWE)2576Kha/0 Tg(PDGFB-PSEN1M146L)2Jhd/0	involves: C57BL/6 * DBA/2 * SJL	MGI:3717259
cx26	Tg(APPSWE)2576Kha/0 Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:3720702
cx27	Tg(APPSWE)2576Kha/? Tg(PDGFB-PSEN1M146L)2Jhd/?	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:3711709
cx28	Tg(APPSWE)2576Kha/0 Tg(PDGFB-PSEN1M146L)2Jhd/0	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:5140748
cx29	Tg(APPSWE)2576Kha/? Tg(EIF1AX-Aldh2*E487K)101Oht/?	involves: C57BL/6 * SJL	MGI:5699096
cx30	Tg(APPSWE)2576Kha/0 Tg(PSEN1)5Dbo/0	involves: C57BL/6 * SJL	MGI:5463430
tg31	Tg(APPSWE)2576Kha/Tg(APPSWE)2576Kha	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:4366449
tg32	Tg(APPSWE)2576Kha/0	FVB.Cg-Tg(APPSWE)2576Kha	MGI:3722308
tg33	Tg(APPSWE)2576Kha/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3029285
tg34	Tg(APPSWE)2576Kha/0	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:3720700
tg35	Tg(APPSWE)2576Kha/0	involves: C57BL/6J * SJL	MGI:3722307
tg36	Tg(APPSWE)2576Kha/0	involves: C57BL/6 * SJL	MGI:3710766

Allelic Composition	Pin1^tm1Tuc/Pin1^tm1Tuc Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129 * 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pin1^tm1Tuc mutation (2 available); any Pin1 mutation (19 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:107132 )

• 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

amyloid beta deposits ( J:107132 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:107132

Allelic Composition	Psen1^tm1Dgf/Psen1^tm1Dgf Tg(APPSWE)2576Kha/?
Genetic Background	involves: 129 * C57BL/6 * CD-1 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Dgf mutation (0 available); any Psen1 mutation (48 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:102425 )

• 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

amyloid beta deposits ( J:102425 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:102425

Allelic Composition	Apoe^{tm1(APOE_i4)Sfu}/Apoe^{tm1(APOE_i4)Sfu} Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^{tm1(APOE_i4)Sfu} mutation (4 available); any Apoe mutation (158 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:121533 )

N	• amyloid beta deposits are scarcely seen at 15-16 months of age compared to the many in single Tg(APPSWE)2576Kha/0 mice

Allelic Composition	Vps35^{Gt(RRK261)Byg}/Vps35⁺ Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Vps35^{Gt(RRK261)Byg} mutation (1 available); any Vps35 mutation (45 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

Increase of amyloid beta deposits and amyloid beta 40 in the hippocampus and cortex of Vps35^{Gt(RRK261)Byg}/Vps35⁺ Tg(APPSWE)2576Kha/0 mice

nervous system

nervous system phenotype ( J:178937 )

N	• mice exhibit normal paired-pulse facilitation and inhibitory synaptic transmission

amyloid beta deposits ( J:178937 )

• in the hippocampus and cerebral cortex

• greater accumulation than in Tg(APPSWE)2576Kha mice

impaired synaptic plasticity ( J:178937 )

• accelerated compared to in Tg(APPSWE)2576Kha mice

abnormal excitatory postsynaptic potential ( J:178937 )

• field excitatory postsynaptic potential slopes in the CA1 and dentate gyrus are reduced compared to in either single heterozygotes

reduced AMPA-mediated synaptic currents ( J:178937 )

• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice

reduced NMDA-mediated synaptic currents ( J:178937 )

• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice

reduced long-term potentiation ( J:178937 )

• in the CA1 at 2 months

• worsened at 4 months in the CA1

• however, long term potentiation in the dentate gyrus is normal

abnormal miniature excitatory postsynaptic currents ( J:178937 )

• mice exhibit reduced AMPA and NMDA receptor-mediated miniature excitatory postsynaptic currents in CA1 pyramidal neurons compared with control mice

decreased post-tetanic potentiation ( J:178937 )

• at 4 months in the CA1

behavior/neurological

abnormal spatial learning ( J:178937 )

• 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

amyloid beta deposits ( J:178937 )

• in the hippocampus and cerebral cortex

• greater accumulation than in Tg(APPSWE)2576Kha mice

Allelic Composition	Nos2^tm1Lau/Nos2^tm1Lau Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nos2^tm1Lau mutation (8 available); any Nos2 mutation (67 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:112919 , J:143551 )

• 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)

abnormal hippocampus CA3 region morphology ( J:143551 )

• neuronal loss in hippocampus, subiculum and CA3 is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha

loss of hippocampal neurons ( J:143551 )

• neuronal loss in hippocampus, subiculum and CA3 is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha

abnormal subiculum morphology ( J:143551 )

• neuronal loss in subiculum is significantly greater in double mutant relative to control transgenic Tg(APPSWE)2576Kha

decreased neuron number ( J:143551 )

neuron degeneration ( J:112919 )

• widespread cortical neuron damage

behavior/neurological

abnormal long-term spatial reference memory ( J:143551 )

• higher level of errors in day 2 of radial arm water maze in double mutant relative to single mutants Tg(APPSWE)2576Kha or homozygous Nos^tm1Lau

homeostasis/metabolism

amyloid beta deposits ( J:112919 , J:143551 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:112919

Allelic Composition	Apoe^{tm3(APOE4)Mae}/Apoe^{tm3(APOE4)Mae} Tg(APPSWE)2576Kha/?
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^{tm3(APOE*4)Mae} mutation (3 available); any Apoe mutation (158 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:98636 )

• 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

• 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

cerebral amyloid angiopathy ( J:98636 )

• Amyloid beta deposition starts around 12-15 months of age

• deposition is almost exclusively in cerebral blood vessels

abnormal cerebrospinal fluid amyloid beta 40 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

abnormal cerebrospinal fluid amyloid beta 42 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

homeostasis/metabolism

amyloid beta deposits ( J:98636 )

• 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

• 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

cerebral amyloid angiopathy ( J:98636 )

• Amyloid beta deposition starts around 12-15 months of age

• deposition is almost exclusively in cerebral blood vessels

abnormal cerebrospinal fluid amyloid beta 40 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

abnormal cerebrospinal fluid amyloid beta 42 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:98636

Allelic Composition	Apoe^{tm2(APOE3)Mae}/Apoe^{tm2(APOE3)Mae} Tg(APPSWE)2576Kha/?
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^{tm2(APOE*3)Mae} mutation (2 available); any Apoe mutation (158 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:98636 )

• 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

• deposition delayed until after 12 months of age

• less plaque development than in Tg(APPSWE)2576Kha, Apoe^{tm3(APOE*4Mae} mice

abnormal cerebrospinal fluid amyloid beta 40 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

abnormal cerebrospinal fluid amyloid beta 42 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

homeostasis/metabolism

amyloid beta deposits ( J:98636 )

• 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

• deposition delayed until after 12 months of age

• less plaque development than in Tg(APPSWE)2576Kha, Apoe^{tm3(APOE*4Mae} mice

abnormal cerebrospinal fluid amyloid beta 40 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

abnormal cerebrospinal fluid amyloid beta 42 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

Allelic Composition	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Mpm mutation (4 available); any Psen1 mutation (48 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:175901 )

• mice accumulate more plaques than in Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha mice

homeostasis/metabolism

amyloid beta deposits ( J:175901 )

• mice accumulate more plaques than in Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha mice

Allelic Composition	Psen1^tm1Dgf/Psen1⁺ Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * CD-1 * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Dgf mutation (0 available); any Psen1 mutation (48 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:66147 )

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

gliosis ( J:66147 )

• mutants exhibit enhanced reactive gliosis compared to single Tg(APPSWE)2576Kha mice

homeostasis/metabolism

amyloid beta deposits ( J:66147 )

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

Allelic Composition	Cd40lg^tm1Flv/Cd40lg^tm1Flv Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd40lg^tm1Flv mutation (1 available); any Cd40lg mutation (17 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:80429 )

• no detectable plaques at 12 months of age compared to minimal levels in mice carrying the transgene alone

• 41-51% reduction in beta-amyloid at 16 months as compared to transgene controls

• reduced numbers of large and medium sized plaques in the neocortex and hippocampus

• beta-CTF is reduced relative to alpha-CTF

gliosis ( J:80429 )

• microgliosis and astrocytosis reduced

homeostasis/metabolism

amyloid beta deposits ( J:80429 )

• no detectable plaques at 12 months of age compared to minimal levels in mice carrying the transgene alone

• 41-51% reduction in beta-amyloid at 16 months as compared to transgene controls

• reduced numbers of large and medium sized plaques in the neocortex and hippocampus

• beta-CTF is reduced relative to alpha-CTF

Allelic Composition	Ccr2^tm1Ifc/Ccr2^tm1Ifc Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S4/SvJae * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr2^tm1Ifc mutation (1 available); any Ccr2 mutation (43 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:121703 )

• 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 Ccr2^tm1Ifc homozygotes

nervous system

intracranial hemorrhage ( J:121703 )

abnormal microglial cell physiology ( J:121703 )

• microglia accumulation is impaired compared to in mice expressing Tg(APPSWE)2576Kha

• however, microglial proliferation and responses to beta-amyloid are normal

amyloid beta deposits ( J:121703 )

• at P65 without classic plaques

immune system

abnormal microglial cell physiology ( J:121703 )

• microglia accumulation is impaired compared to in mice expressing Tg(APPSWE)2576Kha

• however, microglial proliferation and responses to beta-amyloid are normal

cardiovascular system

intracranial hemorrhage ( J:121703 )

hematopoietic system

abnormal microglial cell physiology ( J:121703 )

• microglia accumulation is impaired compared to in mice expressing Tg(APPSWE)2576Kha

• however, microglial proliferation and responses to beta-amyloid are normal

homeostasis/metabolism

amyloidosis ( J:121703 )

• 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

amyloid beta deposits ( J:121703 )

• at P65 without classic plaques

Allelic Composition	Ccr2^tm1Ifc/Ccr2⁺ Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S4/SvJae * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr2^tm1Ifc mutation (1 available); any Ccr2 mutation (43 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:121703 )

• 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 Ccr2^tm1Ifc homozygotes

Allelic Composition	Dab1^tm1Bwh/Dab1^tm1Bwh Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dab1^tm1Bwh mutation (0 available); any Dab1 mutation (79 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

abnormal cerebellar foliation ( J:132599 )

• the loss of divisions between some folia is apparent

small cerebellum ( J:132599 )

• the vermis to whole brain ratio is smaller than in Dab1^tm1Bwh homozygotes

Allelic Composition	Appd1^FVB/NCr/Appd1^FVB/NCr Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * FVB/NCr * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Appd1^FVB/NCr mutation (0 available); any Appd1 mutation (0 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:101523 )

Allelic Composition	Appd2^FVB/NCr/Appd2^FVB/NCr Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * FVB/NCr * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Appd2^FVB/NCr mutation (0 available); any Appd2 mutation (0 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:101523 )

Allelic Composition	Ldlr^tm1Her/Ldlr^tm1Her Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ldlr^tm1Her mutation (19 available); any Ldlr mutation (81 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

abnormal response to new environment ( J:114480 )

• fail to show intersession habituation over 3 days of testing in an open field, unlike transgenic mice wild-type for Ldlr

abnormal spatial learning ( J:114480 )

• learning impairment in a Morris water maze at 10 months of age

• impairment not affected by Ldlr genotype

abnormal long-term spatial reference memory ( J:114480 )

• 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

decreased anxiety-related response ( J:114480 )

• make more entries into the open arms of an elevated plus maze on day 2 of testing

hyperactivity ( J:114480 )

• relative to non-transgenic controls

homeostasis/metabolism

amyloidosis ( J:114480 )

• age dependent cerebral amyloidosis

• plaques first appear in the hippocampus and cortex at around 11 months

• progressive accumulation in the brain after 11 months

amyloid beta deposits ( J:114480 )

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

increased circulating cholesterol level ( J:114480 )

• hypercholesterolemia with the increase in the non-HDL fraction

increased circulating LDL cholesterol level ( J:114480 )

• increase is mainly in the LDL fraction

nervous system

amyloid beta deposits ( J:114480 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:114480

Allelic Composition	Slc30a3^tm1Rpa/Slc30a3^tm1Rpa Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc30a3^tm1Rpa mutation (1 available); any Slc30a3 mutation (28 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:76863 )

• 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

decreased brain zinc level ( J:76863 )

• males and females exhibit a decrease in levels of synaptic and total zinc compared to single Tg(APPSWE)2576Kha hemizygotes

homeostasis/metabolism

amyloid beta deposits ( J:76863 )

• 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

decreased brain zinc level ( J:76863 )

• males and females exhibit a decrease in levels of synaptic and total zinc compared to single Tg(APPSWE)2576Kha hemizygotes

Allelic Composition	Psen1^tm1Zhe/Psen1^tm1Zhe Tg(APPSWE)2576Kha/?
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1Zhe mutation (0 available); any Psen1 mutation (48 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:107251 )

• 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

amyloid beta deposits ( J:107251 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:107251

Allelic Composition	Pld2^tm1.1Gdp/Pld2⁺ Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pld2^tm1.1Gdp mutation (1 available); any Pld2 mutation (49 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

behavior/neurological phenotype ( J:166741 )

N	• mice exhibit normal spatial working memory unlike Tg(APPSWE)2576Kha mice

enhanced contextual conditioning behavior ( J:166741 )

• compared to Tg(APPSWE)2576Kha mice

Allelic Composition	Pld2^tm1.1Gdp/Pld2^tm1.1Gdp Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pld2^tm1.1Gdp mutation (1 available); any Pld2 mutation (49 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

behavior/neurological phenotype ( J:166741 )

N	• mice exhibit normal spatial working memory unlike Tg(APPSWE)2576Kha mice

enhanced contextual conditioning behavior ( J:166741 )

• compared to Tg(APPSWE)2576Kha mice

homeostasis/metabolism

abnormal lipid level ( J:166741 )

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

nervous system

abnormal synapse morphology ( J:166741 )

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

Allelic Composition	Hspa4^tm1.1Miv/Hspa4^tm1.1Miv Tg(APPSWE)2576Kha/0
Genetic Background	involves: BALB/cJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hspa4^tm1.1Miv mutation (0 available); any Hspa4 mutation (75 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:164904 )

• many mice die before 7 months of age

nervous system

neurofibrillary tangles ( J:164904 )

• at 6 months, mice develop neurofibril tangles unlike Tg(APPSWE)2576Kha mice

• at 7 months, mice develop senility plaques unlike Tg(APPSWE)2576Kha mice

neurodegeneration ( J:164904 )

• neuron degeneration is more severe than in Tg(APPSWE)2576Kha mice

Allelic Composition	Tg(APPSWE)2576Kha/0 Tg(Prnp-ITM2B/APP695*42)A12Emcg/0
Genetic Background	involves: C3H * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(Prnp-ITM2B/APP695*42)A12Emcg mutation (2 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:101023 )

• 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

abnormal forebrain morphology ( J:101023 )

• mice show enhanced senile plaque pathology in the forebrain at 14.5 months

abnormal hindbrain morphology ( J:101023 )

• mice show elevated insoluble Abeta levels in the hindbrain at 14.5 months

homeostasis/metabolism

amyloidosis ( J:101023 )

• 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

amyloid beta deposits ( J:101023 )

• 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

Allelic Composition	Psen1^tm1.1Tcs/Psen1^tm1.1Tcs Tg(APPSWE)2576Kha/0
Genetic Background	involves: C57BL/6 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Psen1^tm1.1Tcs mutation (0 available); any Psen1 mutation (48 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

abnormal short-term spatial reference memory ( J:175901 )

• at 3 to 4 months in a Y-maze test

nervous system

amyloid beta deposits ( J:175901 )

• beginning at 6 months, earlier than in Tg(APPSWE)2576Kha mice at 12 months

• fewer plaques than in Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSWE)2576Kha mice

astrocytosis ( J:175901 )

• at 9 months

homeostasis/metabolism

amyloid beta deposits ( J:175901 )

• beginning at 6 months, earlier than in Tg(APPSWE)2576Kha mice at 12 months

• fewer plaques than in Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSWE)2576Kha mice

Allelic Composition	Apoe^{tm3(APOE_i3)Sfu}/Apoe^{tm3(APOE_i3)Sfu} Tg(APPSWE)2576Kha/0
Genetic Background	involves: C57BL/6 * C57BL/6N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^{tm3(APOE_i3)Sfu} mutation (0 available); any Apoe mutation (158 available)
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:121533 )

N	• amyloid beta deposits are scarcely seen at 15-16 months of age compared to the many in single Tg(APPSWE)2576Kha/0 mice

Allelic Composition	Tg(APPSWE)2576Kha/0 Tg(PDGFB-PSEN1M146L)2Jhd/0
Genetic Background	involves: C57BL/6 * DBA/2 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(PDGFB-PSEN1M146L)2Jhd mutation (0 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:68670 )

• 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

abnormal astrocyte morphology ( J:68670 )

• 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

gliosis ( J:68670 )

• activated microglia accumulate around amyloid beta deposits from ~ 3 months; number of glia increases with age and amyloid accumulation

astrocytosis ( J:68670 )

• activated astrocytes accumulate around amyloid deposits in frontal cortex of 3 month old mice

homeostasis/metabolism

amyloidosis ( J:68670 )

amyloid beta deposits ( J:68670 )

• 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

• 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

Allelic Composition	Tg(APPSWE)2576Kha/0 Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0
Genetic Background	involves: C57BL/6 * DBA/2 * SJL * SW

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(Prnp-MAPT*P301L)JNPL3Hlmc mutation (3 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

decreased grooming behavior ( J:100965 )

hunched posture ( J:100965 )

paraparesis ( J:100965 )

• progressive hindlimb weakness is observed

decreased vocalization ( J:100965 )

• reduced

nervous system

amyloid beta deposits ( J:100965 )

• 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

neurofibrillary tangles ( J:100965 )

• 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

tau protein deposits ( J:100965 )

• 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

gliosis ( J:100965 )

• as severe as astrocytosis in ventral diencepalon, hindbrain, and spinal cord

astrocytosis ( J:100965 )

• increase observed in limbic areas with the most NFTs

abnormal neuron morphology ( J:100965 )

• 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

neuron degeneration ( J:100965 )

• 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

abnormal eye physiology ( J:100965 )

• increased eye irritation

homeostasis/metabolism

amyloid beta deposits ( J:100965 )

• deposits contain both Abeta1-40 and Abeta1-42 peptides

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:100965

Allelic Composition	Tg(APPSWE)2576Kha/? Tg(PDGFB-PSEN1M146L)2Jhd/?
Genetic Background	involves: C57BL/6 * DBA/2 * SJL * SW

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(PDGFB-PSEN1M146L)2Jhd mutation (0 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:80429 )

• 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

gliosis ( J:80429 )

• microgliosis and astrocytosis reduced in the hippocampus, and entorhinal cortex

• astrocytosis also reduced in the cingulated cortex

homeostasis/metabolism

amyloid beta deposits ( J:80429 )

• 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

Allelic Composition	Tg(APPSWE)2576Kha/0 Tg(PDGFB-PSEN1M146L)2Jhd/0
Genetic Background	involves: C57BL/6 * DBA/2 * SJL * SW

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(PDGFB-PSEN1M146L)2Jhd mutation (0 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

renal/urinary system

abnormal renal glomerulus morphology ( J:174270 )

• 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

amyloidosis ( J:174270 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:174270

Allelic Composition	Tg(APPSWE)2576Kha/? Tg(EIF1AX-Aldh2*E487K)101Oht/?
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(EIF1AX-Aldh2*E487K)101Oht mutation (0 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:219346 )

• mutants begin dying by 120 days of age and death rate accelerates after 240 days compared to either single mutant

growth/size/body

decreased body weight ( J:219346 )

• mutants weigh less than wild-type mice and single Tg(EIF1AX-Aldh2*E487K)101Oht mice, but exhibit no weight differences from single Tg(APPSWE)2576Kha mice

behavior/neurological

abnormal object recognition memory ( J:219346 )

• in the object recognition test, exploratory preference for the novel object is lower at 3 months of age compared to wild-type mice or either single mutant, and is lower at 6 months of age compared to wild-type mice or single Tg(EIF1AX-Aldh2*E487K)101Oht mice

abnormal spatial working memory ( J:219346 )

• at 3 and 6 months of age, the alternation rate of Y-maze is lower than in wild-type mice or either single mutant

homeostasis/metabolism

amyloid beta deposits ( J:219346 )

• amyloid beta plaques are detected in the brain at 6 months of age, a time when plaques are not seen in single Tg(APPSWE)2576Kha mice

• at 12-15 months of age, more amyloid beta40 and amyloid beta42 plaques are seen than in single Tg(APPSWE)2576Kha mice

nervous system

amyloid beta deposits ( J:219346 )

• amyloid beta plaques are detected in the brain at 6 months of age, a time when plaques are not seen in single Tg(APPSWE)2576Kha mice

• at 12-15 months of age, more amyloid beta40 and amyloid beta42 plaques are seen than in single Tg(APPSWE)2576Kha mice

tau protein deposits ( J:219346 )

• deposition of phosphorylated tau proteins in the brains is increased at 9 months of age compared to single Tg(APPSWE)2576Kha mice

astrocytosis ( J:219346 )

• mutants show a greater number of astrocyte clusters in the CA1 region of the hippocampus and cerebral cortex at 6, 9, and 12 months of age than single Tg(APPSWE)2576Kha mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:219346

Allelic Composition	Tg(APPSWE)2576Kha/0 Tg(PSEN1)5Dbo/0
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(PSEN1)5Dbo mutation (1 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:191088 )

• dense amyloid beta plaques in the cortex and hippocampus, but not in the adrenal medulla

abnormal neuron physiology ( J:191088 )

• 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

amyloid beta deposits ( J:191088 )

• dense amyloid beta plaques in the cortex and hippocampus, but not in the adrenal medulla

abnormal catecholamine level ( J:191088 )

• chromaffin cells release 50% less catecholamine (mean quantal content released per vesicle is halved) in response to a 10 second 70 mM potassium pulse

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:191088

Allelic Composition	Tg(APPSWE)2576Kha/Tg(APPSWE)2576Kha
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:76863 )

• mutants die prematurely; time not specified

Allelic Composition	Tg(APPSWE)2576Kha/0
Genetic Background	FVB.Cg-Tg(APPSWE)2576Kha

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:43446 )

• Background Sensitivity: ~44% of mice die before 150 days of age

behavior/neurological

decreased exploration in new environment ( J:43446 )

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

increased thigmotaxis ( J:43446 )

Allelic Composition	Tg(APPSWE)2576Kha/0
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

behavior/neurological

behavior/neurological phenotype ( J:180385 )

N	• 12 month old mice exhibit normal motor coordination on the rotarod

abnormal eye blink conditioning behavior ( J:180385 )

• 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

abnormal spatial learning ( J:114480 )

• impaired spatial learning in a morris water maze

abnormal long-term spatial reference memory ( J:114480 )

• in a probe trial mice fail to occupy the target quadrant longer than chance indicating memory retention deficits

decreased anxiety-related response ( J:114480 )

• spend more time in the open arms of an elevated plus maze

hyperactivity ( J:114480 )

homeostasis/metabolism

amyloidosis ( J:114480 )

amyloid beta deposits ( J:76863 , J:114480 )

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

increased brain zinc level ( J:76863 )

• females exhibit an increase in levels of synaptic zinc with aging

nervous system

amyloid beta deposits ( J:76863 , J:114480 )

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

increased brain zinc level ( J:76863 )

• females exhibit an increase in levels of synaptic zinc with aging

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:114480 , J:180385

Allelic Composition	Tg(APPSWE)2576Kha/0
Genetic Background	involves: C57BL/6 * DBA/2 * SJL * SW

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

amyloid beta deposits ( J:100965 )

• 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

abnormal renal glomerulus morphology ( J:174270 )

• 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

amyloidosis ( J:174270 )

• 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

amyloid beta deposits ( J:100965 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:174270

Allelic Composition	Tg(APPSWE)2576Kha/0
Genetic Background	involves: C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

mortality/aging

premature death ( J:43446 )

• 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

postnatal lethality ( J:43446 )

• 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)

behavior/neurological

behavior/neurological phenotype ( J:43446 )

N	• Background Sensitivity: mice do not show obvious behavioral abnormalities

Allelic Composition	Tg(APPSWE)2576Kha/0
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

nervous system

microgliosis ( J:159623 )

• at 24 months

amyloid beta deposits ( J:101023 , J:121703 , J:159623 )

• 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)

astrocytosis ( J:159623 )

• at 24 months

cardiovascular system

abnormal blood circulation ( J:119251 )

• 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

microgliosis ( J:159623 )

• at 24 months

immune system

microgliosis ( J:159623 )

• at 24 months

homeostasis/metabolism

amyloidosis ( J:101023 )

• formic acid extractable Abeta40 and Abeta42 levels are dramatically elevated at 14.5 months compared to Tg(Prnp-ITM2B/APP695*42)A12Emcg mice

amyloid beta deposits ( J:101023 , J:121703 , J:159623 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:119251

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