Strain Name:

B6.129S4-Tg(APPSwLon)96Btla/Mmjax

Availability:

Cryopreserved - Ready for recovery     Available at the JAX MMRRC

Use Restrictions Apply, see Terms of Use
This strain is now distributed by the Mutant Mouse Regional Resource Center. Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for ordering information and strain details on B6.129S4-Tg(APPSwLon)96Btla/Mmjax MMRRC Stock Number 034837.
As a designated MMRRC center, The Jackson Laboratory will continue to distribute these mice at the same high health and
quality standards but ordering is exclusively provided through the MMRRC.
Mice hemizygous for this "K670N/M671L + V717I" mutant APP YAC transgene (formerly JAX Stock No. 006406) produce elevated levels of total amyloid-beta and longer amyloid-beta peptides compared to wild-type mice, but not to the extent as observed in a similar strain carrying only the APP (K670N/M671L) mutant transgene (B6.129-Tg(APPSw)40Btla/Mmjax). These mice may be useful in studies of the pathogenesis of Familial Alzheimer's Disease, specifically focusing on the importance of processing at the gamma-secretase site to elevate levels of amyloid-beta 1-42(43).

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

Former Names B6.129S4-Tg(APPSwLon)96Btla/J    (Changed: 11-AUG-11 )
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
GenerationN12+F1pN1
Generation Definitions
 
Donating Investigator Bruce Lamb,   The Cleveland Clinic Foundation

Description
Mice hemizygous for this "K670N/M671L + V717I" mutant APP YAC transgene are viable and fertile. RT-PCR analysis shows hemizygous mice express the mutant human APP mRNA at levels similar to endogenous mouse in brain and peripheral tissues. Further, transcript levels of the most common alternative splice variants (encoding human APP-695, -751 and -770) parallel the endogenous mouse gene expression. The levels of total amyloid-beta and longer amyloid-beta peptides (species terminating at amino acids 42/43) are elevated compared to wild-type mice, but not to the extent as observed in a similar strain carrying only the APP (K670N/M671L) mutant transgene (B6.129-Tg(APPSw)40Btla/Mmjax). These mice may be useful in studies of the pathogenesis of Familial Alzheimer's Disease, specifically focusing on the importance of processing at the gamma-secretase site to elevate levels of amyloid-beta 1-42(43).

Development
A 650 kb YAC transgene containing the entire human amyloid beta (A4) precursor protein (APP) gene, and approximately 250 kb of flanking sequence, was altered to include the Swiss mutation (K670N/M671L) and the London mutation (V717I) associated with Familial Alzheimer's Disease (FAD). This construct was injected into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Founder animals (line J1.96) were found to contain a single copy of this mutant human APP YAC transgene. These mutants were backcrossed to C57BL/6 for at least 11 generations prior to arrival at the MMRRC at The Jackson Laboratory.

Related Strains

Alzheimer's Disease Models
005987   129-Achetm1Loc/J
006409   129S1.129(Cg)-Tg(APPSw)40Btla/Mmjax
008077   129S1/Sv-Bchetm1Loc/J
016198   129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ
014556   129S6/SvEv-Apoetm4Mae/J
006555   A.129(B6)-Tg(APPSw)40Btla/Mmjax
005708   B6.129-Apbb1tm1Quhu/J
004714   B6.129-Bace1tm1Pcw/J
004098   B6.129-Klc1tm1Gsn/J
004193   B6.129-Psen1tm1Mpm/J
003615   B6.129-Psen1tm1Shn/J
005300   B6.129-Tg(APPSw)40Btla/Mmjax
005617   B6.129P-Psen2tm1Bdes/J
002609   B6.129P2-Nos2tm1Lau/J
007685   B6.129P2-Psen1tm1Vln/J
007999   B6.129P2-Sorl1Gt(Ex255)Byg/J
008087   B6.129S1-Bchetm1Loc/J
002509   B6.129S2-Plautm1Mlg/J
005301   B6.129S2-Tg(APP)8.9Btla/J
004163   B6.129S4-Cdk5r1tm1Lht/J
010959   B6.129S4-Grk5tm1Rjl/J
010960   B6.129S4-Grk5tm2Rjl/J
002213   B6.129S4-Ngfrtm1Jae/J
006469   B6.129S4-Tg(PSEN1H163R)G9Btla/J
012564   B6.129S5-Dhcr24tm1Lex/SbpaJ
004142   B6.129S7-Aplp2tm1Dbo/J
004133   B6.129S7-Apptm1Dbo/J
007251   B6.129X1-Mapttm1Hnd/J
013040   B6.Cg-Apoetm1Unc Ins2Akita/J
005642   B6.Cg-Clutm1Jakh/J
005491   B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
009126   B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
005866   B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax
008730   B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
005864   B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
007575   B6.Cg-Tg(CAG-Ngb,-EGFP)1Dgrn/J
016197   B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J
005855   B6.Cg-Tg(Camk2a-Prkaca)426Tabe/J
007004   B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ
004996   B6.Cg-Tg(DBH-Gal)1923Stei/J
007673   B6.Cg-Tg(Gad1-EGFP)3Gfng/J
004662   B6.Cg-Tg(PDGFB-APP)5Lms/J
006293   B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2Mmjax
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/Mmjax
007180   B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J
007182   B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
005999   B6.Cg-Tg(SBE/TK-luc)7Twc/J
012597   B6.Cg-Tg(Thy1-COL25A1)861Yfu/J
007051   B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax
007052   B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax
007049   B6.Cg-Tg(tetO-APPSwInd)885Dbo/Mmjax
009337   B6.FVB-Tg(Prnp-RTN3)2Yanr/J
006394   B6;129-Apba2tm1Sud Apba3tm1Sud Apba1tm1Sud/J
008364   B6;129-Chattm1(cre/ERT)Nat/J
008476   B6;129-Ncstntm1Sud/J
004807   B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax
007605   B6;129P-Psen1tm1Vln/J
005618   B6;129P2-Bace2tm1Bdes/J
008333   B6;129P2-Dldtm1Ptl/J
002596   B6;129P2-Nos2tm1Lau/J
003822   B6;129S-Psen1tm1Shn/J
012639   B6;129S4-Mapttm3(HDAC2)Jae/J
012869   B6;129S6-Apbb2tm1Her/J
006410   B6;129S6-Chattm2(cre)Lowl/J
005993   B6;129S6-Pcsk9tm1Jdh/J
008636   B6;C-Tg(Prnp-APP695*/EYFP)49Gsn/J
007002   B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax
008169   B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J
000231   B6;C3Fe a/a-Csf1op/J
008850   B6;SJL-Tg(Mt1-LDLR)93-4Reh/AgnJ
003378   B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
004462   B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
003741   B6D2-Tg(Prnp-MAPT)43Vle/J
016556   B6N.129-Ptpn5tm1Pjlo/J
018957   B6N.129S6(B6)-Chattm2(cre)Lowl/J
024841   B6N.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J
006554   B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax
012621   C.129S(B6)-Chrna3tm1.1Hwrt/J
002328   C.129S2-Plautm1Mlg/J
003375   C3B6-Tg(APP695)3Dbo/Mmjax
005087   C57BL/6-Tg(Camk2a-IDE)1Selk/J
005086   C57BL/6-Tg(Camk2a-MME)3Selk/J
008833   C57BL/6-Tg(Camk2a-UBB)3413-1Fwvl/J
007027   C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
010800   C57BL/6-Tg(Thy1-PTGS2)300Kand/J
010703   C57BL/6-Tg(Thy1-PTGS2)303Kand/J
005706   C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J
006618   C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J
007677   CB6-Tg(Gad1-EGFP)G42Zjh/J
007072   CByJ.129P2(B6)-Nos2tm1Lau/J
006472   D2.129(B6)-Tg(APPSw)40Btla/Mmjax
007067   D2.129P2(B6)-Apoetm1Unc/J
013719   D2.Cg-Apoetm1Unc Ins2Akita/J
003718   FVB-Tg(GadGFP)45704Swn/J
013732   FVB-Tg(NPEPPS)1Skar/J
013156   FVB-Tg(tetO-CDK5R1*)1Vln/J
015815   FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ
002329   FVB.129S2-Plautm1Mlg/J
003753   FVB/N-Tg(Eno2CDK5R1)1Jdm/J
006143   FVB/N-Tg(Thy1-cre)1Vln/J
008051   NOD.129P2(B6)-Ctsbtm1Jde/RclJ
008390   STOCK Apptm1Sud/J
012640   STOCK Hdac2tm1.2Rdp/J
004808   STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
004779   STOCK Mapttm1(EGFP)Klt/J
014092   STOCK Tg(ACTB-tTA2,-MAPT/lacZ)1Luo/J
014544   STOCK Tg(tetO-ABL1*P242E*P249E)CPdav/J
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(APPSwLon)96Btla/0

        involves: 129S4/SvJae
  • nervous system phenotype
  • *normal* nervous system phenotype
    • no Alzheimer's disease pathology is observed at 2 years of age in homozygotes   (MGI Ref ID J:58050)
    • amyloid beta deposits
      • mice have much higher levels of total A-beta protein and the cleaved A-beta 1-42(43) peptide than Tg(APPSw)40Btla mutant mice or Tg(APP)8.9Btla mice   (MGI Ref ID J:42613)
      • hemizygous mice have 2- to 3-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes   (MGI Ref ID J:58050)
  • homeostasis/metabolism phenotype
  • amyloid beta deposits
    • mice have much higher levels of total A-beta protein and the cleaved A-beta 1-42(43) peptide than Tg(APPSw)40Btla mutant mice or Tg(APP)8.9Btla mice   (MGI Ref ID J:42613)
    • hemizygous mice have 2- to 3-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes   (MGI Ref ID J:58050)

Tg(APPSwLon)96Btla/Tg(APPSwLon)96Btla

        involves: 129S4/SvJae
  • nervous system phenotype
  • *normal* nervous system phenotype
    • no Alzheimer's disease pathology is observed at 2 years of age in homozygotes   (MGI Ref ID J:58050)
    • amyloid beta deposits
      • homzygous mice have 4- to 6-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes   (MGI Ref ID J:58050)
  • homeostasis/metabolism phenotype
  • amyloid beta deposits
    • homzygous mice have 4- to 6-fold higher levels of Abeta1-42 peptide in their brains compared to Tg(PSEN1H163R)G9Btla hemizygotes   (MGI Ref ID J:58050)
View Research Applications

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

Neurobiology Research
Alzheimer's Disease
      strains expressing mutant APP
Neurodegeneration

Research Tools
Neurobiology Research

APP related

Neurobiology Research
Alzheimer's Disease
Neurodegeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(APPSwLon)96Btla
Allele Name transgene insertion 96, Bruce Lamb
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) APPK670N/M671L and APPV717Im; J1.96; K670N/M671L + V717I;
Mutation Made By Bruce Lamb,   The Cleveland Clinic Foundation
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Expressed Gene APP, amyloid beta (A4) precursor protein, human
Promoter APP, amyloid beta (A4) precursor protein, human
General Note The transgene construct was injected into embryonic stem (ES) cells.
Molecular Note A 650 kb YAC transgene containing the entire human amyloid beta (A4) precursor protein gene and approximately 250 kb of flanking sequence was altered to include the Familial Alzheimer's Disease- (FAD-) associated "Swedish" double mutation, APPK670N/M671L, and the "London" mutation, APPV717I. RT-PCR analysis shows hemizygous mice express the mutant human and endogenous mouse APP mRNA at similar levels in brain and peripheral tissues; levels of the most common alternative splice variants (encoding human APP-695, -751 and -770) parallel those of the endogenous mouse transcripts. Levels of total amyloid-beta and of longer amyloid-beta peptides (species terminating at amino acids 42/43) are higher than in wildtype mice, but not as high as in a similar strain carrying only the APPK670N/M671L "Swedish" mutant transgene. [MGI Ref ID J:42613]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(APP), QPCR
Tg(APPSw)40Btla, High Resolution Melting
Tg(APPSw)40Btla, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Tg(APPSwLon)96Btla related

Lamb BA; Bardel KA; Kulnane LS; Anderson JJ; Holtz G; Wagner SL; Sisodia SS; Hoeger EJ. 1999. Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice. Nat Neurosci 2(8):695-7. [PubMed: 10412057]  [MGI Ref ID J:58050]

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 & HusbandryWhen maintaining a live colony, mice are bred by homozygous intercross.

Pricing and Purchasing

Supply Notes


Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


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.

Terms of Use

Terms of Use


General Terms and Conditions


For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"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.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


(6.6)