Overview

Also Known As: APP/PS1

APP/PS1 are double transgenic mice expressing a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9), both directed to CNS neurons. Both mutations are associated with early-onset Alzheimer's disease. These mice may be useful in studying neurological disorders of the brain, specifically Alzheimer's disease, amyloid plaque formation and aging.

Donating Investigator

Dr. David R Borchelt, University of Florida

Genetic overview

Genetic Background	Generation
	?+F15 (2019-01-04 00:00:00)

Tg(APPswe,PSEN1dE9)85Dbo

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Neurobiology Research
Mouse/Human Gene Homologs

View All Research Applications

Details

Detailed Description

APP/PS1 are double transgenic mice expressing a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9), both directed to CNS neurons. Both mutations are associated with early-onset Alzheimer's disease. The "humanized" Mo/HuAPP695swe transgene allows the mice to secrete a human A-beta peptide. Both the transgenic peptide and holoprotein can be detected by antibodies specific for human sequence within this region (Signet Laboratories' monoclonal 6E10 antibody). The included Swedish mutations (K595N/M596L) elevate the amount of A-beta produced from the transgene by favoring processing through the beta-secretase pathway. This "humanized" Mo/HuAPP695swe protein is immunodetected in whole brain protein homogenates. The transgenic mutant human presenilin protein (PS1-dE9), which in high levels displaces detectable endogenous mouse protein, is also immunodetected in whole brain protein homogenates.
The donating investigator reports that transgenic mice develop beta-amyloid deposits in brain by 6 to 7 months of age. Between 6 and 15 months of age, mice exhibit a gender-based disparity in beta-amyloid burden.
Females develop a 5-fold (Aβ₄₂) and 10-fold (Aβ₄₀) increase in beta-amyloid deposits in the cerebellum by 15 months as compared to males. Accumulation of plaques is more abundant in the molecular layer than in the granular layer. In the cortex, the beta-amyloid burden is increased in both sexes in parallel (Ordonez-Guiterrez et al. Jnl Alz Dis 2016).

APP/PS1 hemizygotes on a C57BL/6;C3H genetic background (Stock No. 004462) do not exhibit any seizure phenotype. These animals also display a slight alteration in their tail phenotype (e.g., kinked tail) that is believed to be due to the mixed genetic background of the strain and is not related to transgene expression. This strain does not carry the retinal degeneration allele Pde6b^rd1.

In contrast, APP/PS1 hemizygotes on a C57BL/6J-congenic background (see Stock No. 005864) exhibit seizure activity. Specifically, hemizygous mice on the C57BL/6 background (N9B6) exhibit a high incidence of seizures, as detected by video-EEG. 25% of transgenic mice, 3 to 3.5 months in age, exhibit at least 1 seizure. By 4.5 months of age, seizure incidence increases to 55%. 10-15% mortality is reported for transgenic mice on the congenic (N9) C57BL/6 background (Minkeviciene et al. J Neurosci. 2009). At 17-18 weeks of age, hemizygous mice on the congenic C57BL/6J background (N13) exhibit epileptiform discharges as detected by video-EEG. Mortality was 38% (6/16) and some mutant mice experienced spontaneous seizures during the experiments. Antiepileptic drugs (carbamazepine, phenytoin, valproate) reduce the frequency of spontaneous electrographic epileptiform discharges (Ziyatdinova et al. Epilepsy Res 2011).

Development

Two expression plasmids (Mo/HuAPP695swe and PS1-dE9) were designed to each be controlled by independent mouse prion protein (PrP) promoter elements, directing transgene expression predominantly to CNS neurons. The Mo/HuAPP695swe transgene expresses a "humanized" mouse amyloid beta (A4) precursor protein gene modified at three amino acids to reflect the human residues and further modified to contain the K595N/M596L (also called K670N/M671L) mutations linked to familial Alzheimers. The PS1-dE9 transgene expresses a mutant human presenilin 1 carrying the exon-9-deleted variant (PSEN1dE9) associated with familial Alzheimer's disease. These constructs were coinjected into (C57BL/6 x C3H)F2 pronuclei and insertion of the transgenes occured at a single locus. Founder line 85 was obtained and the resulting colony was maintained as a hemizygote.

Expression Data

Expressed Gene	APP, amyloid beta precursor protein, human
Expressed Gene	PSEN1, presenilin 1, human
Site of Expression

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Reiserer RS; Harrison FE; Syverud DC; McDonald MP. 2007. Impaired spatial learning in the APP + PSEN1DeltaE9 bigenic mouse model of Alzheimer's disease. Genes Brain Behav 6(1):54-65PubMed: 17233641 MGI: J:116798
Jankowsky JL; Slunt HH; Ratovitski T; Jenkins NA; Copeland NG; Borchelt DR. 2001. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17(6):157-65PubMed: 11337275 MGI: J:78664
Jankowsky JL; Fadale DJ; Anderson J; Xu GM; Gonzales V; Jenkins NA; Copeland NG; Lee MK; Younkin LH; Wagner SL; Younkin SG; Borchelt DR. 2004. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(2):159-70PubMed: 14645205 MGI: J:87691

View All References

Genetics

Tg(APPswe,PSEN1dE9)85Dbo

Allele Symbol: Tg(APPswe,PSEN1dE9)85Dbo

Allele Name	transgene insertion 85, David R Borchelt
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	transgene insertion 85, David R Borchelt; Tg(APPswe,PSEN1dE9)85Dbo
Gene Symbol and Name	Tg(APPswe,PSEN1dE9)85Dbo, transgene insertion 85, David R Borchelt
Gene Synonym(s)	APPswe/PS1dE9; APdE9; APP/PS1; Mo/Hu APPswe PS1dE9
Promoter	Prn, prion protein readthrough transcript, mouse, laboratory
Expressed Gene	APP, amyloid beta precursor protein, human
Expressed Gene	PSEN1, presenilin 1, human
Strain of Origin	(C57BL/6 x C3H)F2
Chromosome	9
General Note	Mice carrying this double transgene develop beta-amyloid deposits in the brain by 6 to 7 months of age.
Molecular Note	Two transgenes inserted at a single locus in Chromosome 9 between Arpp21 and Pdcd6ip. Each transgene is controlled by the mouse prion promoter and contains a cDNA sequence. In one transgene the cDNA encodes a chimeric amyloid beta (A4) precursor protein (APPswe). In the second transgene the cDNA encodes the "DeltaE9" mutation of human presenilin 1. The DeltaE9 mutation of the human presenilin 1 gene is a deletion of exon 9 and corresponds to a form of early-onset Alzheimer's disease. The amyloid beta precursor protein coding sequences were altered by replacing mouse sequence encoding three amino acids of the A-beta domain with the human coding sequence for these residues. The chimeric amyloid beta (A4) precursor protein sequence was then further modified to encode the Swedish mutations K595N/M596L found in human. Both the transgenic peptide and holoprotein are detected by Signet Laboratories' monoclonal 6E10 antibody, which is specific for human sequence within this region. Human presenilin protein, which in high levels displaces detectable endogenous mouse protein, is immunodetected in the double transgenic mouse in whole brain protein homogenates. Human amyloid precursor protein is also immunodetected in these mice in whole brain protein homogenates. Transgene insertion occurred on Chr 9, causing a 1 bp duplication.
Mutations Made By	Dr. David Borchelt, University of Florida

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Alzheimer's Disease
  - Presenilin mutants
  - APP and PSEN1 mutants
  - strains expressing mutant APP
- Epilepsy
  - electroconvulsive seizures
- Neurodegeneration
- Behavioral and Learning Defects
Mouse/Human Gene Homologs
- Alzheimer's

Genotype: Tg(APPswe,PSEN1dE9)85Dbo related

Neurobiology Research
- Alzheimer's Disease

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H * C57BL/6

homeostasis/metabolism phenotype

amyloidosis
- increase in circulating amyloid beta protein levels

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - mutants exhibit normal body weight, blood glucose, plasma insulin levels, nonfasting blood glucose and nonfasting plasma insulin, and normal glucose and insulin tolerance, indicating normal glucose homeostasis and insulin sensitivity

nervous system phenotype
- Normal - striatal volume is similar in both transgenic and wild-type at either 6 or 12 months of age

nervous system phenotype

abnormal medium spiny neuron morphology
- nuclei of medium spiny stellate neurons in both 6 and 12 month old transgenics are smaller and darker than wild-type

decreased neuron number
- numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics

neuron degeneration
- numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
- reduced neuron density is observed in striatum of 12, but not 6, month old transgenics

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax

behavior/neurological phenotype

abnormal spatial learning
- 6 month old mutants exhibit slower visuospatial learning than control mice
- in the visuospatial re-learning test performed at 9, 11, 13, 15, and 18 months of age, mutants exhibit a decrease in the speed of re-learning the task compared to controls
- performance in a morris water maze declines between 3 and 12 months of age
- severely impaired performance in a morris water maze with much longer latencies to reach a hidden platform

convulsive seizures
- Background Sensitivity - premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background

impaired contextual conditioning behavior
- Normal - 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the contextual fear conditioning tests
- Normal - 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in contextual conditioning behavior
- Normal - however, VO-OHpic treatment does not affect auditory-cued fear conditioning (hippocampal-independent task), exploratory activity or basal freezing behavior
- mice exhibit decreased freezing to context

impaired passive avoidance behavior

impaired spatial learning
- Normal - 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the novel object-location task
- Normal - 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in spatial learning tasks
- mice exhibit impaired behavior in the novel object location task

homeostasis/metabolism phenotype

amyloid beta deposits
- at 2 months of age carriers are indistinguishable from C57BL/6J controls, but at 4 months of age very small plaques are found in the cortex, and at 6 months of age plaques are evident in the cortex and hippocampus
- Background Sensitivity - there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background

mammalian phenotype

taste/olfaction phenotype
- Normal - mutants do not exhibit Alzheimer's disease-related impairments in olfactory performance in tests based on an operant conditioning procedure and in tests based on a habituation/dishabituation procedure

mortality/aging

premature death
- about 40% of mice are lost by 12 months of age

nervous system phenotype

abnormal CNS synaptic transmission
- basal synaptic transmission is lower in hippocampal slices
- VO-OHpic treatment does not rescue the lower basal synaptic transmission

amyloid beta deposits
- at 2 months of age carriers are indistinguishable from C57BL/6J controls, but at 4 months of age very small plaques are found in the cortex, and at 6 months of age plaques are evident in the cortex and hippocampus
- Background Sensitivity - there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background

astrocytosis

axon degeneration
- axon degeneration and synapse loss

convulsive seizures
- Background Sensitivity - premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background

reduced long term potentiation
- Normal - semi-chronic treatment with VO-OHpic fully rescues LTP levels in hippocampal slices

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo

behavior/neurological phenotype

convulsive seizures
- Normal - despite the increased lethal seizures, the electroconvulsive threshold is not decreased relative to DBA/2J controls
- Background Sensitivity - on the DBA/2J background hemizygotes that die prematurely are found in a lethal seizure pose of clenched front limbs and stretched out hind limbs consistent with the audiogenic seizure-induced death inherent in DBA/2J, but the percentage of hemizygotes found dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
- Background Sensitivity - und dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.

nervous system phenotype

amyloid beta deposits
- Background Sensitivity - although hemizygotes do have some ThioS+ plaque deposition in the cortex, there are far fewer plaques than are found in hemizygotes on the C57BL/6J background (average 10 per section versus 58 per section)

convulsive seizures
- Normal - despite the increased lethal seizures, the electroconvulsive threshold is not decreased relative to DBA/2J controls
- Background Sensitivity - on the DBA/2J background hemizygotes that die prematurely are found in a lethal seizure pose of clenched front limbs and stretched out hind limbs consistent with the audiogenic seizure-induced death inherent in DBA/2J, but the percentage of hemizygotes found dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
- Background Sensitivity - und dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.

microgliosis
- cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls

hematopoietic system phenotype

microgliosis
- cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls

homeostasis/metabolism phenotype

amyloid beta deposits
- Background Sensitivity - although hemizygotes do have some ThioS+ plaque deposition in the cortex, there are far fewer plaques than are found in hemizygotes on the C57BL/6J background (average 10 per section versus 58 per section)

immune system phenotype

microgliosis
- cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls

mammalian phenotype

nervous system phenotype
- Normal - no significant differences are found between hemizygotes and DBA/2J in neuron number in the three different regions of the cortex at 6 months of age, indicating no increase in neuronal cell loss, and the number of cortical astrocytes is normal

mortality/aging

premature death
- There is a much higher rate of premature death in hemizygotes on the DBA/2J background than on the C57BL/6J background, although hemizygotes that survive beyond 6 months of age do not have a high rate of premature death thereafter

Genotype: Hc¹/Hc¹ Tg(APPswe,PSEN1dE9)85Dbo/0
D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo

behavior/neurological phenotype

convulsive seizures
- Background Sensitivity - despite the presence of functional hemolytic complement these mice have the same rate of lethal seizures as transgenics with the non-functional DBA/2J allele

homeostasis/metabolism phenotype

amyloid beta deposits
- Background Sensitivity - the complement pathway does not impact plaque deposition in the cortex, the number of plaques is the same as that in transgene carriers with the DBA/2J allele of Hc

mammalian phenotype

nervous system phenotype
- Normal - no significant differences are found in cortical neuron number in complement deficient versus functional transgene carriers

mortality/aging

premature death

nervous system phenotype

amyloid beta deposits
- Background Sensitivity - the complement pathway does not impact plaque deposition in the cortex, the number of plaques is the same as that in transgene carriers with the DBA/2J allele of Hc

convulsive seizures
- Background Sensitivity - despite the presence of functional hemolytic complement these mice have the same rate of lethal seizures as transgenics with the non-functional DBA/2J allele

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H/HeH * C57BL/6JNju

behavior/neurological phenotype

abnormal olfactory behavior
- in the buried food test, mice need more time to find the hidden food than wild-type mice indicating impaired olfactory performance
- in the olfactory discrimination test, mice show decreases in the numbers of correct olfactory discrimination responses per trial at 3-4 months, 6-7 months, and 9-10 months of age

abnormal spatial reference memory
- in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice require longer to find the platform, indicating that spatial memory impairments begin at 6-7 months of age

impaired spatial learning
- in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice show decreased crossing plate times in the probe trial indicating that spatial discrimination learning impairments begin at 6-7 months of age

homeostasis/metabolism phenotype

amyloid beta deposits
- mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age

nervous system phenotype

abnormal action potential
- mitral cells in 3-4 and 9-10 month old mice exhibit a higher spontaneous firing rate of spontaneous action potential indicating the hyperactivation of mitral cells

abnormal asymmetric synapse morphology
- the presynaptic and postsynaptic membrane structures of asymmetric synapses (excitatory synapses) in the olfactory bulb are damaged

abnormal olfactory bulb external plexiform layer morphology
- Normal - however, laminar organization of the olfactory bulb is normal
- mice exhibit a wider synaptic cleft in the external plexiform layer

abnormal olfactory bulb granule cell morphology
- the dendritic spine density of granule cells is reduced in the olfactory bulb

abnormal postsynaptic density morphology
- thickness of the postsynaptic density in olfactory bulb asymmetric synapses is thinner in 3-4, 6-7, and 9-10 month old mice

abnormal symmetric synapse morphology
- mice exhibit a wider synaptic cleft in the external plexiform layer of symmetric synapses

abnormal synapse morphology

abnormal synaptic transmission
- 3-4 and 9-10 month old mice exhibit increased gamma, low-gamma, and high-gamma oscillations and firing rates of mitral cells in the olfactory bulb external plexiform layer
- Normal - local application of the GABA(A)R agonist muscimol nearly abolishes the aberrant increase in gamma oscillations in the external plexiform layer at advanced stages of disease while a GABA(A)R antagonist bicuculline increased the gamma oscillations

abnormal synaptic vesicle morphology
- synaptic vesicles of olfactory bulb asymmetric synapses exhibit unclear and broken membrane structure and blurred boundaries at 6-7 and 9-10 months of age

amyloid beta deposits
- mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age

decreased dendritic spine density
- immature spine density tends to decline at 3-4 and 6-7 months of age and is reduced at 9-10 months of age
- mature spine density is the same as in wild-type mice at 3-4 months of age but is decreased in 6-7 and 9-10 month old mice
- the dendritic spine density of granule cells is reduced in the olfactory bulb

The following phenotype relates to a compound genotype created using this strain

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H/HeJ * C57BL/6J

behavior/neurological phenotype

abnormal spatial reference memory
- 13 month old transgenic mice commit more errors in the water maze than controls, at 7 months of age both groups test similarly
- transgenic mice exhibit a 4-5% higher preference for the arm of the radial arm water maze that held the platform on the previous day

impaired coordination
- 14 month old transgenic mice exhibit a reduced ability to maintain balance on a rotarod

growth/size/body region phenotype

decreased body weight
- at 14 months, transgenics weigh less than controls

homeostasis/metabolism phenotype

amyloid beta deposits
- deposits observed in hippocampus by 6 months of age
- occasional deposits can be found in mice as young as 6 months of age
- plaques are abundant in hippocampus and cortex by 9 months of age
- ratio of amyloid beta peptide 40:42 is 0.50:1

nervous system phenotype

amyloid beta deposits
- deposits observed in hippocampus by 6 months of age
- occasional deposits can be found in mice as young as 6 months of age
- plaques are abundant in hippocampus and cortex by 9 months of age
- ratio of amyloid beta peptide 40:42 is 0.50:1

reduced long term potentiation
- transient long term potentiation (t-LTP) is reduced in transgenics and is age-independent

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax

behavior/neurological phenotype

abnormal spatial learning
- transgenic mice fed sucrose water failed to learn Morris water maze test after 5 days of training
- water-fed transgenic mice retained some learning ability over 5 day test period, but did not perform as well in the water maze test as non-transgenic controls

increased fluid intake
- mice fed sucrose water exhibited increased water consumption

nervous system phenotype

amyloid beta deposits
- amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
- deposits are more extensive in females
- exhibits an overall increase in soluble and insoluble amyloid beta peptide 40 and 42 between 4 and 12 months
- insoluble amyloid beta42 is increased 2-fold in cerebrum of sucrose-fed mice as compared to water-fed control
- level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age
- plaques are restricted to cortex and hippocampus at time points up to 12 months of age
- plaques increase in number and size over time
- senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months of age
- sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks
- total amyloid beta levels are increased by 3.6 fold in sucrose fed mice

cerebral amyloid angiopathy
- amyloid deposition is observed in leptomeningeal vasculature
- exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months

cardiovascular system phenotype

vasculature congestion

growth/size/body region phenotype

increased body weight
- mice fed sucrose water consistently gained weight over study time period (2 months- 8 months)
- sucrose-fed mice increased body weight by 17% over water-fed controls

homeostasis/metabolism phenotype

amyloid beta deposits
- amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
- deposits are more extensive in females
- exhibits an overall increase in soluble and insoluble amyloid beta peptide 40 and 42 between 4 and 12 months
- insoluble amyloid beta42 is increased 2-fold in cerebrum of sucrose-fed mice as compared to water-fed control
- level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age
- plaques are restricted to cortex and hippocampus at time points up to 12 months of age
- plaques increase in number and size over time
- senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months of age
- sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks
- total amyloid beta levels are increased by 3.6 fold in sucrose fed mice

amyloidosis

cerebral amyloid angiopathy
- amyloid deposition is observed in leptomeningeal vasculature
- exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months

impaired glucose tolerance
- mice fed sucrose water displayed an impaired glucose tolerance as compared to water-fed control

increased circulating cholesterol level
- total cholesterol, but not HDL, levels are increased 30% in mice fed sucrose water as compared to water-fed control

increased circulating insulin level
- fasting plasma insulin levels are increased 3 fold in mice fed sucrose water as compared to water-fed control

increased circulating triglyceride level
- elevated plasma triglyceride levels observed in females at 15 weeks of age

References

Reiserer RS; Harrison FE; Syverud DC; McDonald MP. 2007. Impaired spatial learning in the APP + PSEN1DeltaE9 bigenic mouse model of Alzheimer's disease. Genes Brain Behav 6(1):54-65PubMed: 17233641 MGI: J:116798
Jankowsky JL; Slunt HH; Ratovitski T; Jenkins NA; Copeland NG; Borchelt DR. 2001. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17(6):157-65PubMed: 11337275 MGI: J:78664
Jankowsky JL; Fadale DJ; Anderson J; Xu GM; Gonzales V; Jenkins NA; Copeland NG; Lee MK; Younkin LH; Wagner SL; Younkin SG; Borchelt DR. 2004. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13(2):159-70PubMed: 14645205 MGI: J:87691

Additional References

Fukui H; Diaz F; Garcia S; Moraes CT. 2007. Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease Proc Natl Acad Sci U S A 104(35):14163-8PubMed: 17715058 MGI: J:123812
Sood A; Warren Beach J; Webster SJ; Terry AV; Buccafusco JJ. 2007. The effects of JWB1-84-1 on memory-related task performance by amyloid Abeta transgenic mice and by young and aged monkeys. Neuropharmacology 53(5):588-600PubMed: 17698153 MGI: J:124366
You M; Pan Y; Liu Y; Chen Y; Wu Y; Si J; Wang K; Hu F. 2018. Royal Jelly Alleviates Cognitive Deficits and beta-Amyloid Accumulation in APP/PS1 Mouse Model Via Activation of the cAMP/PKA/CREB/BDNF Pathway and Inhibition of Neuronal Apoptosis. Front Aging Neurosci 10:428PubMed: 30687079 MGI: J:276049
Menal MJ; Jorba I; Torres M; Montserrat JM; Gozal D; Colell A; Pinol-Ripoll G; Navajas D; Almendros I; Farre R. 2018. Alzheimer's Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea. Front Neurol 9:1PubMed: 29403429 MGI: J:277417
Kashyap G; Bapat D; Das D; Gowaikar R; Amritkar RE; Rangarajan G; Ravindranath V; Ambika G. 2019. Synapse loss and progress of Alzheimer's disease -A network model. Sci Rep 9(1):6555PubMed: 31024073 MGI: J:279889
Huang S; Cao X; Zhou Y; Shi F; Xin S; He S; An Y; Gao L; Yang Y; Yu B; Pei G. 2019. An analog derived from phenylpropanoids ameliorates Alzheimer's disease-like pathology and protects mitochondrial function. Neurobiol Aging 80:187-195PubMed: 31203190 MGI: J:281499

Additional - Tg(APPswe,PSEN1dE9)85Dbo related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Generic Psen
- Standard PCR:Generic APP human genomic or cDNA
- Probe:Generic Human PSEN1 cDNA Probe
- Probe:Pde6b^rd1
- Standard PCR:Tg(APPswe,PSEN1dE9)85Dbo-Chr9
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, hemizygotes may be bred with wildtype (noncarrier) siblings. Coat color expected from breeding is black or agouti. While the donating investigator warns that male aggression may require individual housing, there are no such reports of this problem in our colonies at The Jackson Laboratory to date (June 2006).
- Additional Breeding and Husbandry Support
Mating System
- +/+ sibling x Hemizygote
Citation
When using the APP/PS1 mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34829 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX12 (Maximum)

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Questions about Terms of Use

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Strain(s) not available to companies or for-profit entities.

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Email: TechTran@jax.org

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No Liability

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Also Known As: APP/PS1

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(APPswe,PSEN1dE9)85Dbo

Allele Symbol: Tg(APPswe,PSEN1dE9)85Dbo

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Tg(APPswe,PSEN1dE9)85Dbo related

Mammalian Phenotype Terms by Genotype

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0involves: C3H * C57BL/6

homeostasis/metabolism phenotype

mammalian phenotype

nervous system phenotype

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax

behavior/neurological phenotype

homeostasis/metabolism phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo

behavior/neurological phenotype

nervous system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

mortality/aging

Genotype: Hc1/Hc1 Tg(APPswe,PSEN1dE9)85Dbo/0D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo

behavior/neurological phenotype

homeostasis/metabolism phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0involves: C3H/HeH * C57BL/6JNju

behavior/neurological phenotype

homeostasis/metabolism phenotype

nervous system phenotype

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0involves: C3H/HeJ * C57BL/6J

behavior/neurological phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

nervous system phenotype

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax

behavior/neurological phenotype

nervous system phenotype

cardiovascular system phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Tg(APPswe,PSEN1dE9)85Dbo related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H * C57BL/6

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo

Genotype: Hc¹/Hc¹ Tg(APPswe,PSEN1dE9)85Dbo/0
D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H/HeH * C57BL/6JNju

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H/HeJ * C57BL/6J

Genotype: Tg(APPswe,PSEN1dE9)85Dbo/0
B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax