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Strain Name:

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

Stock Number:

004462

Availability:

Level 4

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General Terms and Conditions
Additional Licensing and Use Restrictions

Former Name      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 )
Genes & Alleles   APP;   PSEN1;   Prnp;   Tg(APPswe,PSEN1dE9)85Dbo;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Mating System+/+ sibling x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator David Borchelt,   McKnight Brain Inst, Univ of Florida
GenerationN1F10 (20-DEC-06)

Strain 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 6 to 7 months of age. These mice may be useful in studies of neurological disorders of the brain, specifically Alzheimers disease, amyloid plaque formation, and aging.

Strain 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.

Related Disease (OMIM) Terms

Alzheimer Disease 3
Alzheimer Disease; AD
Mammalian Phenotype Terms assigned by genotype

Tg(APPswe,PSEN1dE9)85Dbo/0

        involves: C3H/HeJ * C57BL/6J
  • nervous system phenotype
  • amyloid beta deposits (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
  • other phenotype
  • amyloid beta deposits (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

Tg(APPswe,PSEN1dE9)85Dbo/0

        B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J
  • nervous system phenotype
  • amyloid beta deposits (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 (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 (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 (J:129021)
    • mice fed sucrose water exhibited increased water consumption
  • homeostasis/metabolism phenotype
  • impaired glucose tolerance (J:129021)
    • mice fed sucrose water displayed an impaired glucose tolerance as compared to water-fed control
  • increased circulating cholesterol level (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 (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 (J:113199)
    • elevated plasma triglyceride levels observed in females at 15 weeks of age
  • cardiovascular system phenotype
  • vasculature congestion (J:113200)
  • other phenotype
  • amyloidosis (J:129021)
    • amyloid beta deposits (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 (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 (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

Gene & Allele Details

Allele Symbol Tg(APPswe,PSEN1dE9)85Dbo
Allele Name transgene insertion 85, David R Borchelt
Common Name(s) APP/PS1; APPswe/PS1dE9; 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 APP, amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease), human
Expressed Gene PSEN1, presenilin 1 (Alzheimer disease 3), 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. [J:78664]

Control Information

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

Genotyping Protocols

Tg(APPswe)
Tg(APPswe)
Tg(PSEN1)

Colony Maintenance

Breeding & HusbandryWhen 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).
Diet Information LabDiet® 5K52/5K67

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)

View Strains carrying other alleles of APP     (14 strains)

View Strains carrying other alleles of PSEN1     (4 strains)

View Strains carrying other alleles of Prnp     (16 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.

Animal Health Reports

Room Number           AX1

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)
Alzheimer's Disease (Presenilin mutants)
Alzheimer's Disease (strains expressing mutant APP)
Alzheimer's Disease
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

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]  [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]  [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]  [J:116798]

Additional References

Price and Supply Information

Strain Name: B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J
Stock Number: 004462

Price Details

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Supply Details

Standard SupplyLevel 4. Up to 10 mice. Larger quantities or custom orders arranged upon request. Expected delivery up to one-three months.
Supply Notes Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available.
Strains that must be genotyped are not available until five to seven weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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

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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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