Strain Name:

B6.129S2-Tg(APP)8.9Btla/J

Stock Number:

005301

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation>N11+N1p
Generation Definitions
 
Donating Investigator Bruce Lamb,   The Cleveland Clinic Foundation

Description
These transgenic mice express all mRNA and protein isoforms of the wild-type human amyloid beta (A4) precursor protein, APP. The transgene expression level is equivalent to the level of endogenous mouse amyloid beta (A4) precursor protein (in the homozygous state). The expression pattern of the various protein isoforms of human APP mimics endogenous mouse gene expression patterns. These mice serve as a model for dosage imbalance for APP that occurs in Down syndrome and also provide a unique model to examine the regulation of APP isoforms, APP processing and amyloid beta metabolism and regulation.

Development
A 650 kb YAC transgene containing entire human APP gene (and approximately 350 kb flanking sequence) was transfected into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Founder animals were backcrossed to C57BL/6J for 11 generations.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

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View Alzheimer's Disease Models     (109 strains)

View Strains carrying other alleles of APP     (16 strains)

Additional Web Information

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 provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Alzheimer Disease; AD
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Cerebral Amyloid Angiopathy, App-Related   (APP)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Tg(APP)8.9Btla/Tg(APP)8.9Btla

        involves: 129S2/SvPas
  • behavior/neurological phenotype
  • abnormal locomotor activation
    • transgenic mice display more spontaneous locomotor activity than controls; activity is higher than in Tg(APP)8.9Btla or Tg(SOD1)51Yg mice   (MGI Ref ID J:96742)
  • abnormal short term object recognition memory
    • at 5.5 months of age, mice do not appear to recall platform position from the previous day of training and show a lower learning rate over subsequent trials   (MGI Ref ID J:96742)
    • impairment observed at 10 months of age   (MGI Ref ID J:96742)
  • abnormal spatial learning
    • at 9 months, a delay of learning process in Morris water maze is observed compared to controls   (MGI Ref ID J:96742)
  • decreased anxiety-related response
    • mice spend less time per entry into dark arms than controlsmice spend less time per entry into dark arms than controls   (MGI Ref ID J:96742)
    • mice exit dark side of dark-light box more often than controls   (MGI Ref ID J:96742)
  • increased exploration in new environment
    • exploratory behavior is increased for both familiar and novel objects   (MGI Ref ID J:96742)
  • vision/eye phenotype
  • *normal* vision/eye phenotype
    • little or no perturbation of the retinas structure or cornea is observed   (MGI Ref ID J:80534)
    • abnormal lens morphology
      • numerous bodies with circular profiles are present in all lens sections examined   (MGI Ref ID J:80534)
      • circles are present in lenses from mice >6 months of age; circles are 1-5 um in diameter   (MGI Ref ID J:80534)
      • lenses from 6 and 16 month-old mice contain swollen cortical fiber cells and lens plaques   (MGI Ref ID J:80534)
      • fiber cell nuclei are disorganized in the outer cortical region compared to wild-type   (MGI Ref ID J:80534)
      • lens degeneration is variable in severity and onset; in some cases, one lens is more severely affected than the other side   (MGI Ref ID J:80534)
      • abnormal lens fiber morphology
        • individual fiber cells are irregularly shaped and fiber cell arrays are misaligned   (MGI Ref ID J:80534)
        • lens fiber cell membranes are morphologically abnormal   (MGI Ref ID J:80534)
        • mice display age-related fiber cell degeneration and cortical plaque formation   (MGI Ref ID J:80534)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • no Abeta peptides are detected in 5 month old mice   (MGI Ref ID J:96742)
View Research Applications

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

APP related

Neurobiology Research
Alzheimer's Disease
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(APP)8.9Btla
Allele Name transgene insertion 8.9, Bruce Lamb
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) APPYAC; Py8.9; Tg(APP)C9.24Jgh; hABetaPP; hAPP-YAC;
Mutation Made By Bruce Lamb,   The Cleveland Clinic Foundation
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Expressed Gene APP, amyloid beta (A4) precursor protein, human
Promoter APP, amyloid beta (A4) precursor protein, human
Molecular Note A 650 kb YAC containing the entire human APP gene and 350 kb of flanking sequence was randomly integerated into ES cells. Southern blot analysis confirmed that construct rearrangement did not occur and that the animals carried a single copy of the intacttransgene. Quantitative RT-PCR analysis of transgenic and wild-type mice revealed that the levels of transgenic human alternate transcripts corresponded with those of the endogenous alternative transcripts. The human APP promoter drives expression in the brain, heart, kidney and testes. [MGI Ref ID J:80947]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(APP), QPCR
Tg(APP), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lamb BT; Sisodia SS; Lawler AM; Slunt HH; Kitt CA; Kearns WG; Pearson PL; Price DL; Gearhart JD. 1993. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected] Nat Genet 5(1):22-30. [PubMed: 8220418]  [MGI Ref ID J:80947]

Additional References

Tg(APP)8.9Btla related

Alpar A; Ueberham U; Bruckner MK; Arendt T; Gartner U. 2006. The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice. Int J Dev Neurosci 24(2-3):133-40. [PubMed: 16384682]  [MGI Ref ID J:129235]

Alpar A; Ueberham U; Seeger G; Arendt T; Gartner U. 2007. Effects of wild-type and mutant human amyloid precursor protein on cortical afferent network. Neuroreport 18(12):1247-50. [PubMed: 17632276]  [MGI Ref ID J:123722]

Chen J; Herrup K. 2012. Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid and H2O2-induced stress. PLoS One 7(3):e33177. [PubMed: 22413000]  [MGI Ref ID J:186926]

Frederikse PH; Ren XO. 2002. Lens Defects and Age-Related Fiber Cell Degeneration in a Mouse Model of Increased AbetaPP Gene Dosage in Down Syndrome. Am J Pathol 161(6):1985-90. [PubMed: 12466113]  [MGI Ref ID J:80534]

Harris-Cerruti C; Kamsler A; Kaplan B; Lamb B; Segal M; Groner Y. 2004. Functional and morphological alterations in compound transgenic mice overexpressing Cu/Zn superoxide dismutase and amyloid precursor protein [correction]. Eur J Neurosci 19(5):1174-90. [PubMed: 15016076]  [MGI Ref ID J:96742]

Kornecook TJ; McKinney AP; Ferguson MT; Dodart JC. 2010. Isoform-specific effects of apolipoprotein E on cognitive performance in targeted-replacement mice overexpressing human APP. Genes Brain Behav 9(2):182-92. [PubMed: 20002203]  [MGI Ref ID J:170794]

Lamb BT; Call LM; Slunt HH; Bardel KA; Lawler AM; Eckman CB; Younkin SG; Holtz G; Wagner SL; Price DL; Sisodia SS; Gearhart JD. 1997. Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet 6(9):1535-41. [PubMed: 9285791]  [MGI Ref ID J:42613]

Lee S; Varvel NH; Konerth ME; Xu G; Cardona AE; Ransohoff RM; Lamb BT. 2010. CX3CR1 deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer's disease mouse models. Am J Pathol 177(5):2549-62. [PubMed: 20864679]  [MGI Ref ID J:166257]

Moreau PH; Bott JB; Zerbinatti C; Renger JJ; Kelche C; Cassel JC; Mathis C. 2013. ApoE4 confers better spatial memory than apoE3 in young adult hAPP-Yac/apoE-TR mice. Behav Brain Res 243:1-5. [PubMed: 23291160]  [MGI Ref ID J:197161]

Salehi A; Delcroix JD; Belichenko PV; Zhan K; Wu C; Valletta JS; Takimoto-Kimura R; Kleschevnikov AM; Sambamurti K; Chung PP; Xia W; Villar A; Campbell WA; Kulnane LS; Nixon RA; Lamb BT; Epstein CJ; Stokin GB; Goldstein LS; Mobley WC. 2006. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51(1):29-42. [PubMed: 16815330]  [MGI Ref ID J:122937]

Seo H; Isacson O. 2010. The hAPP-YAC transgenic model has elevated UPS activity in the frontal cortex similar to Alzheimer's disease and Down's syndrome. J Neurochem 114(6):1819-26. [PubMed: 20698932]  [MGI Ref ID J:164692]

Vidal R; Ghetti B. 2012. Generation of a novel murine model of Abeta deposition based on the expression of human wild-type amyloid precursor protein gene. Prion 6(4):346-9. [PubMed: 22874668]  [MGI Ref ID J:197584]

Vidal R; Sammeta N; Garringer HJ; Sambamurti K; Miravalle L; Lamb BT; Ghetti B. 2012. The Psen1-L166P-knock-in mutation leads to amyloid deposition in human wild-type amyloid precursor protein YAC transgenic mice. FASEB J 26(7):2899-910. [PubMed: 22459153]  [MGI Ref ID J:187475]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryThe strain is maintained as a homozygote.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory's Genotype Promise

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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