Description

Strain Information

Former Names B6C3-Tg(APPswe, PSEN1dE9)85Dbo/J    (Changed: 01-FEB-06 ) B6C3-Tg(APP695)85Dbo Tg(PSEN1)85Dbo    (Changed: 15-DEC-04 ) B6C3-Tg(APP695)85Dbo Tg(PSEN1)85Dbo/J    (Changed: 15-DEC-04 ) Mo/Hu APPswe PS1dE9    (Changed: 15-DEC-04 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System +/+ sibling x Hemizygote         (Female x Male)   31-MAY-08 Species laboratory mouse Generation N1F10 (20-DEC-06)   Donating Investigator David Borchelt,   McKnight Brain Inst, Univ of Florida

Description
Double transgenic mice express 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 six to seven months of age. These animals also display a slight alteration in their tail phenotype that is believed to be due to the mixed genetic background of the strain and is not related to transgene expression. These mice may be useful in studies of neurological disorders of the brain, specifically Alzheimer's disease, amyloid plaque formation, and aging.

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 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 B6C3HF2 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 by crossing transgenic mice to B6C3F1/J mice.

Control Information

	Control
	Noncarrier
	100010 B6C3F1/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(APPswe,PSEN1dE9)85Dbo allele

005864

B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J

View Strains carrying   Tg(APPswe,PSEN1dE9)85Dbo     (1 strain)

Strains carrying other alleles of APP

008609	129S1.129(Cg)-Tg(APPSw)40Btla/2J
006409	129S1.129(Cg)-Tg(APPSw)40Btla/J
006555	A.129(B6)-Tg(APPSw)40Btla/J
005300	B6.129-Tg(APPSw)40Btla/J
005301	B6.129S2-Tg(APP)8.9Btla/J
006406	B6.129S4-Tg(APPSwLon)96Btla/J
009126	B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/J
004662	B6.Cg-Tg(PDGFB-APP)5Lms/J
006293	B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J
006006	B6.Cg-Tg(Prnp-APP)A-2Dbo/J
006005	B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/J
007049	B6.Cg-Tg(tetO-APPSwInd)885Dbo/J
006004	B6C3-Tg(tetO-APPSwInd)885Dbo/J
007027	C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/J
006472	D2.129(B6)-Tg(APPSw)40Btla/J

View Strains carrying other alleles of APP     (15 strains)

Strains carrying other alleles of PSEN1

006469	B6.129S4-Tg(PSEN1H163R)G9Btla/J
005866	B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J
004807	B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/J
003378	B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
006554	B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/J

View Strains carrying other alleles of PSEN1     (5 strains)

Strains carrying other alleles of Prnp

003960	129S6-Tg(Prnp-GFP/cre)1Blw/J
005866	B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J
006006	B6.Cg-Tg(Prnp-APP)A-2Dbo/J
008596	B6.Cg-Tg(Prnp-Abca1)EHol/J
006005	B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/J
007180	B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J
007182	B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
010700	B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J
007002	B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
008169	B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J
004479	B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J
003378	B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
003627	B6C3-Tg(HD82Gln)81Dbo/J
008075	B6CBA(FVB)-Tg(Prnp-TBP*)105Xjl/J
008083	B6CBA(FVB)-Tg(Prnp-TBP*)13Xjl/J
008216	B6CBA(FVB)-Tg(Prnp-TBP*)71-16Xjl/J
003741	B6D2-Tg(Prnp-MAPT)43Vle/J
003375	C3B6-Tg(APP695)3Dbo/J
008212	STOCK Smn1tm1Msd Tg(Prnp-SMN)92Ahmb Tg(SMN2)89Ahmb/J

View Strains carrying other alleles of Prnp     (19 strains)

Additional Web Information

JAX^® NOTES, Fall 2003; 491. Erratum to 'Alzheimer's Disease-Related Strain' JAX^® Notes No. 488, Winter 2002.
JAX^® NOTES, Winter 2002; 488. Alzheimer's Disease-Related Strain.
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Alzheimer Disease 3 -
	Alzheimer Disease; AD -

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Tg(APPswe,PSEN1dE9)85Dbo/0

        involves: C3H/HeJ * C57BL/6J

• nervous system phenotype
• amyloid beta deposits (MGI Ref ID J:87691)
  • plaques are abundant in hippocampus and cortex by 9 months of age
  • occasional deposits can be found in mice as young as 6 months of age
  • ratio of amyloid beta peptide 40:42 is 0.50:1
  • deposits observed in hippocampus by 6 months of age
• reduced long term potentiation (MGI Ref ID J:139071)
  • transient long term potentiation (t-LTP) is reduced in transgenics and is age-independent
• other phenotype
• amyloid beta deposits (MGI Ref ID J:87691)
  • plaques are abundant in hippocampus and cortex by 9 months of age
  • occasional deposits can be found in mice as young as 6 months of age
  • ratio of amyloid beta peptide 40:42 is 0.50:1
  • deposits observed in hippocampus by 6 months of age
• behavior/neurological phenotype
• abnormal spatial reference memory (MGI Ref ID J:139071)
  • 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
  • 13 month old transgenic mice commit more errors in the water maze than controls, at 7 months of age both groups test similarly
• impaired coordination (MGI Ref ID J:139071)
  • 14 month old transgenic mice exhibit a reduced ability to maintain balance on a rotarod
• growth/size phenotype
• decreased body weight (MGI Ref ID J:139071)
  • at 14 months, transgenics weigh less than controls

Tg(APPswe,PSEN1dE9)85Dbo/0

        B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J

• nervous system phenotype
• amyloid beta deposits (MGI Ref ID J:113199)
  • sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks
  • deposits are more extensive in females
  • level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age
  • senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months 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
  • 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
  • total amyloid beta levels are increased by 3.6 fold in sucrose fed mice
  • amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
• cerebral amyloid angiopathy (MGI Ref ID J:113200)
  • exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
  • amyloid deposition is observed in leptomeningeal vasculature
• behavior/neurological phenotype
• abnormal spatial learning (MGI Ref ID J:129021)
  • 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 drinking behavior (MGI Ref ID J:129021)
  • mice fed sucrose water exhibited increased water consumption
• homeostasis/metabolism phenotype
• impaired glucose tolerance (MGI Ref ID J:129021)
  • mice fed sucrose water displayed an impaired glucose tolerance as compared to water-fed control
• increased circulating cholesterol level (MGI Ref ID J:129021)
  • total cholesterol, but not HDL, levels are increased 30% in mice fed sucrose water as compared to water-fed control
• increased circulating insulin level (MGI Ref ID J:129021)
  • fasting plasma insulin levels are increased 3 fold in mice fed sucrose water as compared to water-fed control
• increased circulating triglyceride level (MGI Ref ID J:113199)
  • elevated plasma triglyceride levels observed in females at 15 weeks of age
• cardiovascular system phenotype
• vasculature congestion (MGI Ref ID J:113200)
• other phenotype
• amyloidosis (MGI Ref ID J:129021)
• amyloid beta deposits (MGI Ref ID J:113199)
  • sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks
  • deposits are more extensive in females
  • level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age
  • senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months 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
  • 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
  • total amyloid beta levels are increased by 3.6 fold in sucrose fed mice
  • amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
• cerebral amyloid angiopathy (MGI Ref ID J:113200)
  • exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
  • amyloid deposition is observed in leptomeningeal vasculature
• growth/size phenotype
• increased body weight (MGI Ref ID J:129021)
  • 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

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tg(APPswe,PSEN1dE9)85Dbo/0

        Background Not Specified

• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:145530)
  • striatal volume is similar in both transgenic and wild-type at either 6 or 12 months of age
• abnormal medium spiny neuron morphology (MGI Ref ID J:145530)
  • nuclei of medium spiny stellate neurons in both 6 and 12 month old transgenics are smaller and darker than wild-type
• decreased neuron number (MGI Ref ID J:145530)
  • numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
• neuron degeneration (MGI Ref ID J:145530)
  • 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

View Research Applications

Research Applications

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

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Alzheimer's Disease
      APP and PSEN1 mutants
      Presenilin mutants
      strains expressing mutant APP
Behavioral and Learning Defects
Neurodegeneration

APP related

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Neurodegeneration

Tg(APPswe,PSEN1dE9)85Dbo related

Neurobiology Research
Alzheimer's Disease

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(APPswe,PSEN1dE9)85Dbo
Allele Name		transgene insertion 85, David R Borchelt
Allele Type		Transgenic (random, expressed)
Common Name(s)		APP/PS1; APPswe/PS1dE9; APdE9; Mo/Hu APPswe PS1dE9; Tg(APPswe,PSEN1dE9)85Dbo;
Mutation Made By		David Borchelt,   McKnight Brain Inst, Univ of Florida
Strain of Origin		(C57BL/6 x C3H)F2
Expressed Gene		PSEN1, presenilin 1, human
Expressed Gene		APP, amyloid beta (A4) precursor protein, human
Promoter		Prnp, prion protein, mouse, laboratory
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. 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. [MGI Ref ID J:78664]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Tg(APP) Melt Curve Analysis, Melt Curve Analysis
Tg(PSEN1), Melt Curve Analysis
Generic Pde6b, Melt Curve Analysis
Tg(PSEN1), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

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):159-70. [PubMed: 14645205]  [MGI Ref ID J:87691]

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):157-65. [PubMed: 11337275]  [MGI Ref ID J:78664]

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):54-65. [PubMed: 17233641]  [MGI Ref ID J:116798]

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):14163-8. [PubMed: 17715058]  [MGI Ref ID 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):588-600. [PubMed: 17698153]  [MGI Ref ID J:124366]

Tg(APPswe,PSEN1dE9)85Dbo related

Bernardo A; Harrison FE; McCord M; Zhao J; Bruchey A; Davies SS; Jackson Roberts L nd; Mathews PM; Matsuoka Y; Ariga T; Yu RK; Thompson R; McDonald MP. 2009. Elimination of GD3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice. Neurobiol Aging 30(11):1777-91. [PubMed: 18258340]  [MGI Ref ID J:152957]

Burgess BL; McIsaac SA; Naus KE; Chan JY; Tansley GH; Yang J; Miao F; Ross CJ; van Eck M; Hayden MR; van Nostrand W; St George-Hyslop P; Westaway D; Wellington CL. 2006. Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma. Neurobiol Dis 24(1):114-27. [PubMed: 16899370]  [MGI Ref ID J:113199]

Butovsky O; Kunis G; Koronyo-Hamaoui M; Schwartz M. 2007. Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model. Eur J Neurosci 26(2):413-6. [PubMed: 17623022]  [MGI Ref ID J:127277]

Cao D; Lu H; Lewis TL; Li L. 2007. Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem 282(50):36275-82. [PubMed: 17942401]  [MGI Ref ID J:129021]

Choi SH; Leight SN; Lee VM; Li T; Wong PC; Johnson JA; Saraiva MJ; Sisodia SS. 2007. Accelerated Abeta deposition in APPswe/PS1deltaE9 mice with hemizygous deletions of TTR (transthyretin). J Neurosci 27(26):7006-10. [PubMed: 17596449]  [MGI Ref ID J:122976]

Crouch PJ; Hung LW; Adlard PA; Cortes M; Lal V; Filiz G; Perez KA; Nurjono M; Caragounis A; Du T; Laughton K; Volitakis I; Bush AI; Li QX; Masters CL; Cappai R; Cherny RA; Donnelly PS; White AR; Barnham KJ. 2009. Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation. Proc Natl Acad Sci U S A 106(2):381-6. [PubMed: 19122148]  [MGI Ref ID J:143873]

Ding Y; Qiao A; Wang Z; Goodwin JS; Lee ES; Block ML; Allsbrook M; McDonald MP; Fan GH. 2008. Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer's disease transgenic mouse model. J Neurosci 28(45):11622-34. [PubMed: 18987198]  [MGI Ref ID J:143199]

Du J; Sun B; Chen K; Fan L; Wang Z. 2009. Antagonist of peroxisome proliferator-activated receptor gamma induces cerebellar amyloid-beta levels and motor dysfunction in APP/PS1 transgenic mice. Biochem Biophys Res Commun 384(3):357-61. [PubMed: 19422805]  [MGI Ref ID J:150592]

Du J; Sun B; Chen K; Zhang L; Liu S; Gu Q; Fan L; Zhao N; Wang Z. 2009. Metabolites of cerebellar neurons and hippocampal neurons play opposite roles in pathogenesis of Alzheimer's disease. PLoS ONE 4(5):e5530. [PubMed: 19436731]  [MGI Ref ID J:148883]

Garcia-Alloza M; Borrelli LA; Rozkalne A; Hyman BT; Bacskai BJ. 2007. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model J Neurochem 102(4):1095-104. [PubMed: 17472706]  [MGI Ref ID J:120785]

Garcia-Alloza M; Robbins EM; Zhang-Nunes SX; Prucell SM; Betensky RA; Raju S; Prada C; Greenberg SM; Bacskai BJ; Frosch MP. 2006. Charaterization of amyloid deposition in the APPswe/PS2dE9 mouse model of Alzheimer disease Neurobiol Dis 24(3):516-524. [PubMed: 17029828]  [MGI Ref ID J:113200]

Goto Y; Niidome T; Hongo H; Akaike A; Kihara T; Sugimoto H. 2008. Impaired muscarinic regulation of excitatory synaptic transmission in the APPswe/PS1dE9 mouse model of Alzheimer's disease. Eur J Pharmacol 583(1):84-91. [PubMed: 18282567]  [MGI Ref ID J:134791]

Halford RW; Russell DW. 2009. Reduction of cholesterol synthesis in the mouse brain does not affect amyloid formation in Alzheimer's disease, but does extend lifespan. Proc Natl Acad Sci U S A 106(9):3502-6. [PubMed: 19204288]  [MGI Ref ID J:146447]

Hickman SE; Allison EK; El Khoury J. 2008. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci 28(33):8354-60. [PubMed: 18701698]  [MGI Ref ID J:138606]

Hirsch-Reinshagen V; Chan JY; Wilkinson A; Tanaka T; Fan J; Ou G; Maia LF; Singaraja RR; Hayden MR; Wellington CL. 2007. Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-beta peptide levels in vivo. J Lipid Res 48(4):914-23. [PubMed: 17235115]  [MGI Ref ID J:121674]

Hirsch-Reinshagen V; Maia LF; Burgess BL; Blain JF; Naus KE; McIsaac SA; Parkinson PF; Chan JY; Tansley GH; Hayden MR; Poirier J; Van Nostrand W; Wellington CL. 2005. The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease. J Biol Chem 280(52):43243-56. [PubMed: 16207707]  [MGI Ref ID J:105900]

Ho A; Liu X; Sudhof TC. 2008. Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer's disease. J Neurosci 28(53):14392-400. [PubMed: 19118172]  [MGI Ref ID J:142874]

Hooijmans CR; Graven C; Dederen PJ; Tanila H; van Groen T; Kiliaan AJ. 2007. Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain Res 1181:93-103. [PubMed: 17916337]  [MGI Ref ID J:127348]

Hooijmans CR; Rutters F; Dederen PJ; Gambarota G; Veltien A; van Groen T; Broersen LM; Lutjohann D; Heerschap A; Tanila H; Kiliaan AJ. 2007. Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD). Neurobiol Dis 28(1):16-29. [PubMed: 17720508]  [MGI Ref ID J:134833]

Jankowsky JL; Younkin LH; Gonzales V; Fadale DJ; Slunt HH; Lester HA; Younkin SG; Borchelt DR. 2007. Rodent A beta modulates the solubility and distribution of amyloid deposits in transgenic mice. J Biol Chem 282(31):22707-20. [PubMed: 17556372]  [MGI Ref ID J:124804]

Kang JE; Lim MM; Bateman RJ; Lee JJ; Smyth LP; Cirrito JR; Fujiki N; Nishino S; Holtzman DM. 2009. Amyloid-{beta} Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science :. [PubMed: 19779148]  [MGI Ref ID J:154074]

Kanninen K; Heikkinen R; Malm T; Rolova T; Kuhmonen S; Leinonen H; Yla-Herttuala S; Tanila H; Levonen AL; Koistinaho M; Koistinaho J. 2009. Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 106(38):16505-10. [PubMed: 19805328]  [MGI Ref ID J:153226]

Kanninen K; Malm TM; Jyrkkanen HK; Goldsteins G; Keksa-Goldsteine V; Tanila H; Yamamoto M; Yla-Herttuala S; Levonen AL; Koistinaho J. 2008. Nuclear factor erythroid 2-related factor 2 protects against beta amyloid. Mol Cell Neurosci 39(3):302-13. [PubMed: 18706502]  [MGI Ref ID J:142109]

Knafo S; Venero C; Merino-Serrais P; Fernaud-Espinosa I; Gonzalez-Soriano J; Ferrer I; Santpere G; DeFelipe J. 2009. Morphological alterations to neurons of the amygdala and impaired fear conditioning in a transgenic mouse model of Alzheimer's disease. J Pathol 219(1):41-51. [PubMed: 19449368]  [MGI Ref ID J:151904]

Koffie RM ; Meyer-Luehmann M ; Hashimoto T ; Adams KW ; Mielke ML ; Garcia-Alloza M ; Micheva KD ; Smith SJ ; Kim ML ; Lee VM ; Hyman BT ; Spires-Jones TL. 2009. Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci U S A 106(10):4012-7. [PubMed: 19228947]  [MGI Ref ID J:146596]

Kuchibhotla KV; Lattarulo CR; Hyman BT; Bacskai BJ. 2009. Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323(5918):1211-5. [PubMed: 19251629]  [MGI Ref ID J:145934]

Lalonde R; Kim HD; Fukuchi K. 2004. Exploratory activity, anxiety, and motor coordination in bigenic APPswe + PS1/DeltaE9 mice. Neurosci Lett 369(2):156-61. [PubMed: 15450687]  [MGI Ref ID J:93096]

Lalonde R; Kim HD; Maxwell JA; Fukuchi K. 2005. Exploratory activity and spatial learning in 12-month-old APP(695)SWE/co+PS1/DeltaE9 mice with amyloid plaques. Neurosci Lett 390(2):87-92. [PubMed: 16169151]  [MGI Ref ID J:104569]

Li T; Wen H; Brayton C; Laird FM; Ma G; Peng S; Placanica L; Wu TC; Crain BJ; Price DL; Eberhart CG; Wong PC. 2007. Moderate reduction of gamma-secretase attenuates amyloid burden and limits mechanism-based liabilities. J Neurosci 27(40):10849-59. [PubMed: 17913918]  [MGI Ref ID J:125592]

Liang X; Wang Q; Hand T; Wu L; Breyer RM; Montine TJ; Andreasson K. 2005. Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer's disease. J Neurosci 25(44):10180-7. [PubMed: 16267225]  [MGI Ref ID J:102728]

Machova E; Jakubik J; Michal P; Oksman M; Iivonen H; Tanila H; Dolezal V. 2008. Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice. Neurobiol Aging 29(3):368-78. [PubMed: 17140703]  [MGI Ref ID J:135055]

Malm TM; Iivonen H; Goldsteins G; Keksa-Goldsteine V; Ahtoniemi T; Kanninen K; Salminen A; Auriola S; Van Groen T; Tanila H; Koistinaho J. 2007. Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting beta-amyloid burden. J Neurosci 27(14):3712-21. [PubMed: 17409235]  [MGI Ref ID J:119404]

Matsuda S; Giliberto L; Matsuda Y; McGowan EM; D'Adamio L. 2008. BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate. J Neurosci 28(35):8668-76. [PubMed: 18753367]  [MGI Ref ID J:138796]

Melnikova T; Savonenko A; Wang Q; Liang X; Hand T; Wu L; Kaufmann WE; Vehmas A; Andreasson KI. 2006. Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern. Neuroscience 141(3):1149-62. [PubMed: 16753269]  [MGI Ref ID J:111748]

Meyer-Luehmann M; Mielke M; Spires-Jones TL; Stoothoff W; Jones P; Bacskai BJ; Hyman BT. 2009. A reporter of local dendritic translocation shows plaque- related loss of neural system function in APP-transgenic mice. J Neurosci 29(40):12636-40. [PubMed: 19812338]  [MGI Ref ID J:153880]

Meyer-Luehmann M; Spires-Jones TL; Prada C; Garcia-Alloza M; de Calignon A; Rozkalne A; Koenigsknecht-Talboo J; Holtzman DM; Bacskai BJ; Hyman BT. 2008. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 451(7179):720-4. [PubMed: 18256671]  [MGI Ref ID J:132628]

Minkeviciene R; Ihalainen J; Malm T; Matilainen O; Keksa-Goldsteine V; Goldsteins G; Iivonen H; Leguit N; Glennon J; Koistinaho J; Banerjee P; Tanila H. 2008. Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice. J Neurochem 105(3):584-94. [PubMed: 18042177]  [MGI Ref ID J:134481]

Minkeviciene R; Rheims S; Dobszay MB; Zilberter M; Hartikainen J; Fulop L; Penke B; Zilberter Y; Harkany T; Pitkanen A; Tanila H. 2009. Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 29(11):3453-62. [PubMed: 19295151]  [MGI Ref ID J:147045]

Ni Y; Zhao X; Bao G; Zou L; Teng L; Wang Z; Song M; Xiong J; Bai Y; Pei G. 2006. Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med 12(12):1390-6. [PubMed: 17115048]  [MGI Ref ID J:117739]

Ning A; Cui J; To E; Ashe KH; Matsubara J. 2008. Amyloid-beta deposits lead to retinal degeneration in a mouse model of Alzheimer disease. Invest Ophthalmol Vis Sci 49(11):5136-43. [PubMed: 18566467]  [MGI Ref ID J:141764]

O'Leary TP; Brown RE. 2009. Visuo-spatial learning and memory deficits on the Barnes maze in the 16-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease. Behav Brain Res 201(1):120-7. [PubMed: 19428625]  [MGI Ref ID J:148386]

O'Neil JN; Mouton PR; Tizabi Y; Ottinger MA; Lei DL; Ingram DK; Manaye KF. 2007. Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice. J Chem Neuroanat 34(3-4):102-7. [PubMed: 17658239]  [MGI Ref ID J:129903]

Oh ES; Savonenko AV; King JF; Fangmark Tucker SM; Rudow GL; Xu G; Borchelt DR; Troncoso JC. 2009. Amyloid precursor protein increases cortical neuron size in transgenic mice. Neurobiol Aging 30(8):1238-44. [PubMed: 18304698]  [MGI Ref ID J:152955]

Park JH; Gimbel DA; GrandPre T; Lee JK; Kim JE; Li W; Lee DH; Strittmatter SM. 2006. Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid-beta plaque deposition. J Neurosci 26(5):1386-95. [PubMed: 16452662]  [MGI Ref ID J:105196]

Park JH; Widi GA; Gimbel DA; Harel NY; Lee DH; Strittmatter SM. 2006. Subcutaneous Nogo receptor removes brain amyloid-beta and improves spatial memory in Alzheimer's transgenic mice. J Neurosci 26(51):13279-86. [PubMed: 17182778]  [MGI Ref ID J:116775]

Richner M; Bach G; West MJ. 2009. Over expression of amyloid beta-protein reduces the number of neurons in the striatum of APPswe/PS1DeltaE9. Brain Res :. [PubMed: 19245800]  [MGI Ref ID J:145530]

Shaftel SS; Kyrkanides S; Olschowka JA; Miller JN; Johnson RE; O'Banion MK. 2007. Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest 117(6):1595-604. [PubMed: 17549256]  [MGI Ref ID J:122022]

Shemer I; Holmgren C; Min R; Fulop L; Zilberter M; Sousa KM; Farkas T; Hartig W; Penke B; Burnashev N; Tanila H; Zilberter Y; Harkany T. 2006. Non-fibrillar beta-amyloid abates spike-timing-dependent synaptic potentiation at excitatory synapses in layer 2/3 of the neocortex by targeting postsynaptic AMPA receptors. Eur J Neurosci 23(8):2035-47. [PubMed: 16630051]  [MGI Ref ID J:108064]

Sheng JG; Price DL; Koliatsos VE. 2002. Disruption of corticocortical connections ameliorates amyloid burden in terminal fields in a transgenic model of Abeta amyloidosis. J Neurosci 22(22):9794-9. [PubMed: 12427835]  [MGI Ref ID J:134697]

Shi Q; Prior M; He W; Tang X; Hu X; Yan R. 2009. Reduced amyloid deposition in mice overexpressing RTN3 is adversely affected by preformed dystrophic neurites. J Neurosci 29(29):9163-73. [PubMed: 19625507]  [MGI Ref ID J:151798]

Stoltenberg M; Bush AI; Bach G; Smidt K; Larsen A; Rungby J; Lund S; Doering P; Danscher G. 2007. Amyloid plaques arise from zinc-enriched cortical layers in APP/PS1 transgenic mice and are paradoxically enlarged with dietary zinc deficiency. Neuroscience 150(2):357-69. [PubMed: 17949919]  [MGI Ref ID J:130788]

Thomas P; Wang YJ; Zhong JH; Kosaraju S; O'Callaghan NJ; Zhou XF; Fenech M. 2009. Grape seed polyphenols and curcumin reduce genomic instability events in a transgenic mouse model for Alzheimer's disease. Mutat Res 661(1-2):25-34. [PubMed: 19027755]  [MGI Ref ID J:145012]

Town T; Laouar Y; Pittenger C; Mori T; Szekely CA; Tan J; Duman RS; Flavell RA. 2008. Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med 14(6):681-7. [PubMed: 18516051]  [MGI Ref ID J:137043]

Turdi S; Guo R; Huff AF; Wolf EM; Culver B; Ren J. 2009. Cardiomyocyte contractile dysfunction in the APPswe/PS1dE9 mouse model of Alzheimer's disease. PLoS One 4(6):e6033. [PubMed: 19551139]  [MGI Ref ID J:150191]

Volianskis A; Kostner R; Molgaard M; Hass S; Jensen MS. 2008. Episodic memory deficits are not related to altered glutamatergic synaptic transmission and plasticity in the CA1 hippocampus of the APPswe/PS1DeltaE9-deleted transgenic mice model of beta-amyloidosis. Neurobiol Aging :. [PubMed: 18790549]  [MGI Ref ID J:139071]

West MJ; Bach G; Soderman A; Jensen JL. 2009. Synaptic contact number and size in stratum radiatum CA1 of APP/PS1DeltaE9 transgenic mice. Neurobiol Aging 30(11):1756-76. [PubMed: 18336954]  [MGI Ref ID J:152954]

Xu G; Karch C; Li N; Lin N; Fromholt D; Gonzales V; Borchelt DR. 2008. Receptor-associated protein (RAP) plays a central role in modulating Abeta deposition in APP/PS1 transgenic mice. PLoS ONE 3(9):e3159. [PubMed: 18776935]  [MGI Ref ID J:143942]

Yoshiike Y; Kimura T; Yamashita S; Furudate H; Mizoroki T; Murayama M; Takashima A. 2008. GABA(A) receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin. PLoS ONE 3(8):e3029. [PubMed: 18716656]  [MGI Ref ID J:139681]

Zamora E; Handisurya A; Shafti-Keramat S; Borchelt D; Rudow G; Conant K; Cox C; Troncoso JC; Kirnbauer R. 2006. Papillomavirus-like particles are an effective platform for amyloid-beta immunization in rabbits and transgenic mice. J Immunol 177(4):2662-70. [PubMed: 16888028]  [MGI Ref ID J:138349]

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Zhang Q; Zhang X; Chen J; Miao Y; Sun A. 2009. Role of caspase-3 in tau truncation at D421 is restricted in transgenic mouse models for tauopathies. J Neurochem 109(2):476-84. [PubMed: 19200347]  [MGI Ref ID J:149265]

Zhang X; Luhrs KJ; Ryff KA; Malik WT; Driscoll MJ; Culver B. 2009. Suppression of nuclear factor kappa B ameliorates astrogliosis but not amyloid burden in APPswe/PS1dE9 mice. Neuroscience 161(1):53-8. [PubMed: 19286451]  [MGI Ref ID J:152589]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX1

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, hemizygotes may be bred with wildtype siblings. Coat color expected from breeding Black or Agouti. While the donating investigator warns that male aggression may require individual housing, there are no such reports of this problem to date in our colonies at The Jackson Laboratory (Jun 2006).
Mating System	+/+ sibling x Hemizygote         (Female x Male)   31-MAY-08
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply	Level 4. Up to 10 mice. Larger quantities or custom orders arranged upon request. Expected delivery up to one to three months.
Supply Notes	This strain is also available on a B6 congenic background Stock No. 005864 B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Noncarrier
	100010 B6C3F1/J	(approximate)
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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