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Strain Name:

B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J

Stock Number:

006293

Availability:

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Strain Common Names      J20 line;
Genes & Alleles   APP;   PDGFB;   Tg(PDGFB-APPSwInd)20Lms;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Mating SystemInbred x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator Lennart Mucke,   Gladstone Inst of Neurological Disease
GenerationN12+3 (03-JUN-07)

Strain Description
These transgenic mice express a mutant form of the human amyloid protein precursor bearing both the Swedish (K670N/M671L) and the Indiana (V717F) mutations (APPSwInd). Expression of the transgenic insert is directed by the human platelet-derived growth factor beta polypeptide (PDGFB) promoter. Hemizygotes express immunodetectable transgene product in cerebral neurons, with the highest level of expression occurring in the neocortex and hippocampus. Enzyme-linked immunosorbent assay (ELISA) analysis reveals approximate total amyloid beta peptides and 42 amino acid length amyloid beta peptides in neocortical and hippocampal tissue from mutant mice. At 5 to 7 months of age diffuse amyloid beta peptides deposition in the dendate gyrus and neocortex forms. Amyloid deposition is progressive with all transgenic mice exhibiting plaques by age 8 to 10 months. This mutant mouse strain represents a model that may be useful in studies of the pathogenesis of Familial Alzheimer's Disease and possible therapeutic treatments.

Strain Development
A transgenic construct containing the mutant human amyloid protein precursor APPSwInd under the control of human platelet-derived growth factor beta polypeptide, simian sarcoma viral (v-sis) oncogene homolog, (PDGFB) promoter, was injected into C57BL/6 X DBA/2 F2 one-cell embryos. Heterozygous founder animals were bred to C57BL/6 X DBA/2 F1 mice. The resulting transgenic mice were then backcrossed for 12 generations on the C57BL/6J background.

This strain was previously distributed as Stock No. 004661. That strain was found to have undergone a loss of transgenic copy number and consequent delayed onset of the phenotype, so this strain was re-imported from the lab of Dr. Lennart Mucke. Transgenic copy number is assayed using a Multiplex TaqMan assay.

Related Disease (OMIM) Terms

Alzheimer Disease; AD
Mammalian Phenotype Terms assigned by genotype

Tg(PDGFB-APPSwInd)20Lms/0

        B6.D2-Tg(PDGFB-APPSwInd)20Lms
  • nervous system phenotype
  • abnormal neuron morphology (MGI Ref ID J:100954)
    • dystrophic neurites are associated with plaques
  • amyloid beta deposits (MGI Ref ID J:100954)
    • mice develop amyloid peptide deposits by 5-7 months of age
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:100954)
    • mice develop amyloid peptide deposits by 5-7 months of age

Tg(PDGFB-APPSwInd)20Lms/0

        B6.Cg-Tg(PDGFB-APPSwInd)20Lms
  • nervous system phenotype
  • abnormal pyramidal neuron morphology (MGI Ref ID J:118589)
    • at 6 months and 12 to 16 months of age, 30% fewer pyramidal cells in the entorhinal cortex express Reelin than in wild type mice
    • however, no neuron loss is observed

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

Tg(PDGFB-APPSwInd)20Lms/0

        involves: C57BL/6 * DBA/2
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:121330)
    • mice show premature death of unclear etiology with >15% mortality exhibited by 6 months, compared to all other genotypes
    • high rate of premature (6 months or earlier) death
  • behavior/neurological phenotype
  • abnormal long-term object recognition memory (MGI Ref ID J:121330)
    • at 4-7 months of age, mice transgenic mice with wild type Mapt expression take longer to locate the platform in the cued version of the Morris water maze test compared to transgenic mice heterozygous or homozygous for Mapt deletion
  • abnormal spatial learning (MGI Ref ID J:121330)
    • in the hidden platform version of the Morris water maze, non-trangenic controls, regardless of Mapt genotype learn the task over 3 days, whereas transgenic mice with wild-type expression of Mapt show no evidence of learning
    • in probe trials where the platform is removed, mice show no learning, displaying no significantly elevated crossings of the target quadrant after 5 days of training
  • hyperactivity (MGI Ref ID J:121330)
    • mice show hyperactivity in the Y-maze, a new cage, and elevated-plus maze compared to other transgenic mice or non-transgenic controls; this persists in mice 12-16 months of age
  • susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
    • mice are abnormally sensitive to pentylenetetrazole (PTZ)-induced seizures with 20% suffering fatal status epilepticus at a PTZ dose not lethal in non-transgenic controls
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:62290)
    • no amyloid plaques are detected by immunohistochemistry up to the age of 24 months
    • abnormal neurogenesis (MGI Ref ID J:121330)
      • aberrant sprouting of hippocampal axons is observed in transgenic mice
    • abnormal neuron morphology (MGI Ref ID J:121330)
      • mice show neuritic dystrophy around amyloid plaques
    • amyloid beta deposits (MGI Ref ID J:62290)
      • diffuse immunoreactive amyloid deposits detected in dentate gyrus and neocortex of mice aged 5 to 7 months old
      • all mice exhibit plaques by age 8 to 10 months
      • at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous null for Mapt
      • soluble and insoluble Abeta-40 and -42 peptide deposits at 6-10 months
    • neurodegeneration (MGI Ref ID J:62290)
      • neurodegeneration is indicated by an age dependent decrease in density of synaptophysin-immunoreactive presynaptic terminals
    • susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
      • mice are abnormally sensitive to pentylenetetrazole (PTZ)-induced seizures with 20% suffering fatal status epilepticus at a PTZ dose not lethal in non-transgenic controls
  • other phenotype
  • amyloid beta deposits (MGI Ref ID J:62290)
    • diffuse immunoreactive amyloid deposits detected in dentate gyrus and neocortex of mice aged 5 to 7 months old
    • all mice exhibit plaques by age 8 to 10 months
    • at 4-7 months and 14-18 months, Abeta plaque deposition is observed, at levels the same as other transgenics heterozygous null for Mapt
    • soluble and insoluble Abeta-40 and -42 peptide deposits at 6-10 months
  • homeostasis/metabolism phenotype
  • susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
    • mice are abnormally sensitive to pentylenetetrazole (PTZ)-induced seizures with 20% suffering fatal status epilepticus at a PTZ dose not lethal in non-transgenic controls

Gene & Allele Details

Allele Symbol Tg(PDGFB-APPSwInd)20Lms
Allele Name transgene insertion 20, Lennart Mucke
Common Name(s) J20; PDGF-APPSwInd;
Mutation Made By Lennart Mucke,   Gladstone Inst of Neurological Disease
Strain of Origin(C57BL/6 x DBA/2)F2
Expressed Gene APP, amyloid beta (A4) precursor protein, human
Promoter PDGFB, platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog), human
General Note This line is also called line J20.

Diffuse amyloid beta peptides deposition forms in the dendate gyrus and neocortex at 5 to 7 months of age. Amyloid deposition is progressive, with all transgenic mice exhibiting plaques by age 8 to 10 months.

Molecular Note The transgene expresses the mutant human amyloid protein precursor APPSwInd, which bears both the Swedish (K670N/M671L) and the Indiana (V717F) mutations, under the control of the human platelet derived growth factor, B polypeptide (PDGFB) promoter. Hemizygous transgenic mice express immunodetectable transgene product in cerebral neurons, with the highest level of expression occurring in the neocortex and hippocampus. ELISA analysis reveals approximate total amyloid beta peptides and 42 amino acid lengthamyloid beta peptides in neocortical and hippocampal tissue from transgenic mice. [MGI Ref ID J:62290]

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(PDGFB-APP)

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous males are bred to wildtype siblings or to C57BL/6J inbred females. Pups born of carrier females have shown an increased mortality rate in our colonies.
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Tg(PDGFB-APPSwInd)20Lms allele
004661   B6.Cg-Tg(PDGFB-APPSwInd)20Lms/1J
View Strains carrying   Tg(PDGFB-APPSwInd)20Lms     (1 strain)

View Strains carrying other alleles of APP     (14 strains)

Strains carrying other alleles of PDGFB
004662   B6.Cg-Tg(PDGFB-APP)5Lms/J
View Strains carrying other alleles of PDGFB     (1 strain)

Additional Web Information

Congenic Nomenclature
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Animal Health Reports

Room Number           AX11

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 (strains expressing mutant APP)
Alzheimer's Disease
Behavioral and Learning Defects

APP related

Mouse/Human Gene Homologs
Alzheimer's

Neurobiology Research
Neurodegeneration

Tg(PDGFB-APPSwInd)20Lms related

Neurobiology Research
Alzheimer's Disease

References

Selected Reference(s)

Mucke L; Masliah E; Yu GQ; Mallory M; Rockenstein EM; Tatsuno G; Hu K; Kholodenko D; Johnson-Wood K; McConlogue L. 2000. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20(11):4050-8. [PubMed: 10818140]  [MGI Ref ID J:62290]

Additional References

Price and Supply Information

Strain Name: B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J
Stock Number: 006293

Price Details

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Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes AGED MICE WILL BE AVAILABLE.
Limited quantities of 6 month old animals will be available. Cost will be the listed price per animal, plus a charge based on the age of the animal. To register interest in obtaining aged animals, go to the Strain Interest Form.
Usually shipped between four and eight weeks of age.
This strain is included in the Induced Mutant Resource Colony collection.
LicensingSee General Terms and Conditions below for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

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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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