Strain Detail Sheet

Strain Name:
B6J.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/Mmjax
Stock Number:
034836-JAX
Citation ID:
RRID:MMRRC_034836-JAX
Other Names:
PDGF-hAPP695,751,770V171F, KM670/671NL, hAPPJ20
This strain was formerly available as JAX Strain #006293.

Strain Information

Gene Details

PDGFB
Name: platelet derived growth factor subunit B
Type:
Species: Homo sapiens (human)
Chromosome: 22
Zbtb20
Name: zinc finger and BTB domain containing 20
Synonyms: 1300017A20Rik, D16Wsu73e, Zfp288, A930017C21Rik, 7330412A13Rik, HOF
Type: Gene
Species: Mouse
Chromosome: 16
NCBI: 56490
Homologene: 9226
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APP
Name: amyloid beta precursor protein
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Zbtb20Tg(PDGFB-APPSwInd)20Lms
Name: transgene insertion 20, Lennart Mucke
Synonyms: Tg(PDGFB-APP*Swe*Ind)20Lms, hAPPJ20, J20, APP Tg, PDAPP-J20, PDGF-hAPP695,751,770V171F, KM670/671NL, APP/J20, hAPP-J20, PDGF-APPSwInd
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations
This ES cell line carries a random insertion of human, mutated APP driven by human PDGFB promoter; the transgene was found to be inserted into the Zbtb20 gene. The APP variants are commonly referred to as the Swedish and the Indiana mutations

HGVS nomenclature
  • "Swedish" mutation
    • Genbank RefSeq - mRNA: NM_000484.4
    • Genbank RefSeq, protein: NP_000475.1
    • Variant, nucleic acid level: c.2010G>T and c.2011A>C = c.2010_2011inv
    • Variant, amino acid level, predicted: p.Lys670_Met671delinsAsnLeu (p.[K670N;M671L])
      Check this variant: LUMC Mutalyzer
  • "Indiana" mutation
    • Genbank RefSeq - mRNA: NM_000484.4
    • Genbank RefSeq, protein: NP_000475.1
    • Variant, nucleic acid level: c.2149G>T
    • Variant, amino acid level, predicted: p.Val717Phe (p.V717F)
      Check this variant: LUMC Mutalyzer
Genotype Determination

Strain Description

Phenotype
Homozygous: Not evaluated

Hemizygous: 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 five to seven months of age diffuse amyloid beta peptides deposition in the dentate gyrus and neocortex forms. Amyloid deposition is progressive with all transgenic mice exhibiting plaques by age eight to 10 months. Video-EEG monitoring of 4 to 7-month-old hemizygous transgenic mice, N10+ on the C57BL/6J background, reveals hippocampal hyperexcitability and cortical and hippocampal spontaneous nonconvulsive seizures. The mice are immobile, with no myoclonic behavior observed, during the non-convulsive electroencephalographic seizures. Pentylenetetrazole-induced seizures have earlier onset, are more severe and result in more frequent deaths (50% develop fatal status epilepticus) than wild-type controls (PMID:17785178). 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. Pups born of carrier females have shown an increased mortality rate in our colonies. The Donating Researcher has observed an approximately 15% mortality rate in the first 6 months of life.
MeSH Terms
  • Aging/pathology
  • Alzheimer Disease/genetics
  • Amino Acid Sequence
  • Amyloid beta-Peptides/biosynthesis
  • Amyloid beta-Peptides/genetics
  • Amyloid beta-Protein Precursor/genetics
  • Animals
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nerve Degeneration/genetics
  • Peptide Fragments/biosynthesis
  • Peptide Fragments/genetics
  • Plaque, Amyloid/genetics
  • Plaque, Amyloid/metabolism
  • RNA, Messenger/analysis
  • RNA, Messenger/biosynthesis
  • Receptors, Presynaptic/genetics
  • Receptors, Presynaptic/metabolism
  • Synapses/genetics
  • Synapses/physiology
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 backcrossed for 12 generations on the C57BL/6J background.
Suggested Control Mice
Wild-type littermates or C57BL/6J mice

MMRRC Genetic QC

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor
Lennart Mucke, Ph.D., Gladstone Institute of Neurological Disease
Primary Reference
Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000 Jun 1;20(11):4050-8. (Medline PMID: 10818140)

Colony and Husbandry Information

Special Considerations

Pups born of carrier females have shown an increased mortality rate in our colonies. The Donating Researcher has observed an approximately 15% mortality rate in the first 6 months of life.

Health Status Report

Colony's Current Health Status Report

For more information about this colony's health status contact csmmrrc@jax.org

Appearance

Coat Color
Black

Breeding

MMRRC Breeding System
Backcross or Sib-mating
Breeding Scheme(s)
  • Backcross:
    • Wild-type (C57BL/6J) female x Hemizygous male
  • Sib-mating:
    • Wild-type female x Hemizygous male littermate
    • Hemizygous females x Wild-type male littermates is not recommended due to an increased mortality rate.
Generation
N12 (C57BL/6J)
Overall Breeding Performance
Fair

Reproductive Statistics

NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined Undetermined
Homozygotes are fertile: Undetermined Undetermined
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
Undetermined
Recommended wean age
3 weeks

Order Request Information

Availability Level

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Conditions of Distribution

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*		 Units Notes
034836-JAX-HET-F
034836-JAX-HET-M
034836-JAX-WT-F
034836-JAX-WT-M
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
 $218.00 / Non-Profit Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
034836-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.