Phenotypes associated with this allele

• Allele Symbol: Tg(PSEN1dE9)S9Dbo
• Allele Name: transgene insertion S9, David R Borchelt
• Allele ID: MGI:3618599
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax	MGI:4437308
cx2	Sorl1^tm1Tew/Sorl1^tm1Tew Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129 * C3H/HeJ * C57BL/6	MGI:5050413
cx3	Bace1^tm1Pcw/Bace1^tm1Pcw Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J	MGI:3720944
cx4	Bace1^tm1Pcw/Bace1^+ Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J	MGI:3720945
cx5	Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J	MGI:3720946
cx6	Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	involves: C3H/HeJ * C57BL/6J	MGI:3639713
cx7	Tg(APP695)3Dbo/0 Tg(PSEN1dE9)S9Dbo/0	Not Specified	MGI:3837363
tg8	Tg(PSEN1dE9)S9Dbo/0	involves: C3H/HeJ * C57BL/6J	MGI:3618601

Genotype
MGI:4437308

cx1

• Allelic Composition: Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax

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

nervous system

amyloid beta deposits ( J:157228 )

homeostasis/metabolism

amyloid beta deposits ( J:157228 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease 3		DOID:0110042	OMIM:607822	J:157228

Genotype
MGI:5050413

cx2

• Allelic Composition: Sorl1^tm1Tew/Sorl1^tm1Tew; Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: 129 * C3H/HeJ * C57BL/6

nervous system

amyloid beta deposits ( J:142501 )

• amyloid beta levels and amyloid plaque burden are increased at 4.5 and 6 months of age, but not at 12 months of age, compared to transgenic mice wild-type for Sorl1 suggesting an acceleration in accumulation of amyloid beta

• some of the largest differences in amyloid measures are detected in the cerebellum

homeostasis/metabolism

amyloid beta deposits ( J:142501 )

• amyloid beta levels and amyloid plaque burden are increased at 4.5 and 6 months of age, but not at 12 months of age, compared to transgenic mice wild-type for Sorl1 suggesting an acceleration in accumulation of amyloid beta

• some of the largest differences in amyloid measures are detected in the cerebellum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:142501

Genotype
MGI:3720944

cx3

• Allelic Composition: Bace1^tm1Pcw/Bace1^tm1Pcw; Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:123534 )

N • mice perform as well as control mice in platform and probe trials in Morris water maze tasks

decreased anxiety-related response ( J:123534 )

• in open field test, mice are similar to Bace1^tm1Pcw homozygotes, and spend more time in open area at center of field than at periphery

abnormal locomotor activation ( J:123534 )

• swim speed is lower than other genotypes and nontransgenic mice in hidden and visible platform trials

nervous system

nervous system phenotype ( J:123534 )

N • in 12- or 20-month old mice, no amyloid beta (Abeta) aggregation is detected in brains; no amyloid deposits are found

Genotype
MGI:3720945

cx4

• Allelic Composition: Bace1^tm1Pcw/Bace1⁺; Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J

behavior/neurological

abnormal spatial learning ( J:123534 )

abnormal spatial reference memory ( J:123534 )

• mice are significantly impaired in Morris water maze tasks

nervous system

amyloid beta deposits ( J:123534 )

• high level of amyloid beta aggregates are found in brain at 12 months of age

homeostasis/metabolism

amyloidosis ( J:123534 )

• in 12-month old brains, there is a 27% reduction in amyloid beta aggregates compared to transgenic mice that are wild-type for Bace1; there are no significant differences at 20 months

• in 12-month old brains, there is 37% reduction in percentage of brain volume occupied by amyloid beta deposits, but no difference at 20 months

amyloid beta deposits ( J:123534 )

• high level of amyloid beta aggregates are found in brain at 12 months of age

Genotype
MGI:3720946

cx5

• Allelic Composition: Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:123534 )

N

abnormal spatial learning ( J:123534 )

• mice travel shorter distance in open-field and show less activity or excursions into central area; mice remain near periphery of apparatus rather than entering open center of field

abnormal spatial reference memory ( J:123534 )

• 16-18 month-old mice swim farther to find platform and spend less time in platform vicinity than controls

nervous system

amyloid beta deposits ( J:123534 )

• one month following neuron injection with virus expressing short hairpin RNA to silence Bace1, there is a 38% reduction in amyloid beta burden in hippocampus compared to uninjected hippocampus

homeostasis/metabolism

amyloidosis ( J:123534 )

• mice display amyloid beta aggregates at 12 and 20 months

amyloid beta deposits ( J:123534 )

• one month following neuron injection with virus expressing short hairpin RNA to silence Bace1, there is a 38% reduction in amyloid beta burden in hippocampus compared to uninjected hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:123534
Alzheimer's disease 3		DOID:0110042	OMIM:607822	J:123534

Genotype
MGI:3639713

cx6

• Allelic Composition: Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

nervous system

amyloid beta deposits ( J:87691 , J:104236 )

• develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus (J:87691)

• ratio of amyloid beta peptide 40:42 is 0.75:1 (J:87691)

• 150% increase in amyloid beta peptide 42 (J:87691)

• at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex (J:104236)

homeostasis/metabolism

amyloid beta deposits ( J:87691 , J:104236 )

• develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus (J:87691)

• ratio of amyloid beta peptide 40:42 is 0.75:1 (J:87691)

• 150% increase in amyloid beta peptide 42 (J:87691)

• at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex (J:104236)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:123534
Alzheimer's disease 3		DOID:0110042	OMIM:607822	J:123534
Alzheimer's disease 4		DOID:0110040	OMIM:606889	J:123534

Genotype
MGI:3837363

cx7

• Allelic Composition: Tg(APP695)3Dbo/0; Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: Not Specified

nervous system

abnormal microglial cell morphology ( J:139070 )

• increase in microglial cell activity in retina is observed in 12-15 month old transgenics

• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control

• microglia density, but not cell body size, is increased in transgenics

amyloid beta deposits ( J:139070 )

• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age

• plaques have radial branches with a central core

• plaque size ranges from 5-20 um, larger plaques are observed at 15-16 months

• plaques appear earlier in females than in males and increase in number over time

• 100% of females and 75% of males have plaques in retina by 15-16 months

abnormal amacrine cell morphology ( J:139070 )

• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining

vision/eye

abnormal retina morphology ( J:139070 )

• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age

• most plaques (34.7% and 41% respectively) are found in the inner and outer plexiform layers

• thickness of the retinal nuclear layers is similar to control, suggesting that there is no obvious neuronal cell loss

abnormal amacrine cell morphology ( J:139070 )

• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining

abnormal retina inner plexiform layer morphology ( J:139070 )

• thioflavine-S positive plaques are first observed in females in the IPL at 12 months

• plaques are first observed in males at 13 months

• plaques are embedded within IPL cholinergic bands

abnormal retina outer plexiform layer morphology ( J:139070 )

• thioflavine-S positive plaques are first observed in females in the OPL at 12 months

• plaques are first observed in males at 13 months

abnormal eye electrophysiology ( J:139070 )

• amplitudes of a and b waves are decreased in 12-16 month old mice when tested at lower light intensity, but not a higher intensity

• latency and implicit time as determined by ERG measurement are similar to control

immune system

abnormal microglial cell morphology ( J:139070 )

• increase in microglial cell activity in retina is observed in 12-15 month old transgenics

• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control

• microglia density, but not cell body size, is increased in transgenics

hematopoietic system

abnormal microglial cell morphology ( J:139070 )

• increase in microglial cell activity in retina is observed in 12-15 month old transgenics

• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control

• microglia density, but not cell body size, is increased in transgenics

homeostasis/metabolism

amyloid beta deposits ( J:139070 )

• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age

• plaques have radial branches with a central core

• plaque size ranges from 5-20 um, larger plaques are observed at 15-16 months

• plaques appear earlier in females than in males and increase in number over time

• 100% of females and 75% of males have plaques in retina by 15-16 months

Genotype
MGI:3618601

tg8

• Allelic Composition: Tg(PSEN1dE9)S9Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

nervous system

abnormal brain morphology ( J:104147 )

• immunoblotting of of cortical and hippocampal extracts from transgenic mice under conditions that distinguish mouse and human full-length PSEN1 and its endoproteolytic derivatives demonstrates failure of the transgenic protein to undergo endoproteolysis and, instead, accumulation of the full-length mutant human protein in the brain

• endoproteolytic cleavage products of endogenous mouse PSEN1 are 70-90% less abundant in brains of transgenic than of wild-type mice; however, failure of its cleavage does not result in accumulation of the full-length mouse protein

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:104147
Alzheimer's disease 3		DOID:0110042	OMIM:607822	J:104147