Strain Name:
B6.129-Tg(APPSw)40Btla/Mmjax
Stock Number:
034831-JAX
Citation ID:
RRID:MMRRC_034831-JAX
Other Names:
This strain was formerly available as JaxMice stock number 5300. APPK670N/M671L, R1.40 YAC

Gene Information

Transgene: Tg(APPSw)40Btla (Mus musculus (mouse))
Name: transgene insertion 40, Bruce Lamb; transgene insertion 40, Bruce Lamb
Synonyms: Tg(APP*Swe)40Btla, APP, R1.40, APP, R1.40-YAC
Chromosome: unknown
Alteration at locus: Transgenic
Monarch Initiative (Disease and Phenotype Associations): MGI:3510594
ES Cell Line
N/A
Phenotype
Homozygous: These R1.40 transgenic mice express all mRNA and protein isoforms of the human amyloid beta (A4) precursor protein APP containing the Familial Alzheimer Disease (FAD) Swedish mutation K670N/M671L. Transgene expression (mRNA and full-length protein) is two to three fold the endogenous mouse App expression level in the hemizygous state in brain tissue as revealed by RT-PCR and Western Blot analysis. Transgene expression pattern mimics endogenous mouse gene expression patterns. Levels of the beta- secretase generated human APP derivative, C-terminal 13.5kDA fragment, are elevated in brain tissue. ELISA enzyme-linked immunosorbent assay (ELISA) analysis of brain homogenates show a significant increase in total amyloid-beta peptides and 42 amino acid length amyloid beta peptides. By 14 months of age, homozygous mice develop both parenchymal and vascular amyloid beta deposits, which first appear in the frontal cortex and then spread into the hippocampus. The donating investigator reports increased mortality in young homozygous animals (higher incidence in females). 3 to 4 month old transgenic mice, maintained on a C57BL/6J background, exhibit spontaneous seizure-like events (abnormal spiking) in EEG readings, without abnormal behavior and are more susceptible to kainic acid induced seizures (Vogt et al. Neurobiol Aging 2009). These R1.40 transgenic mice may be useful in studying the pathogenesis of Familial Alzheimer's Disease and possible therapeutic treatments.

A publication (Lehman et al. 2003 Hum Mol Genet 12:2949) compares the well characterized B6-R1.40 strain with two additional congenic strains, D2-R1.40 and 129S1-R1.40. While these three congenic strains have similar levels of holo-APP in brain tissue, the levels of brain APP C-terminal fragments (CTFs) vary depending upon genetic background. Brain and plasma levels of amyloid beta-40 and -42 are variable as well (B6-R1.40 > 129S1-R1.40 > D2-R1.40). In addition, the congenic strains exhibited dramatic alterations in the age of onset of amyloid beta deposition; in contrast to 14 month old homozygous B6-R1.40 mice, homozygous D2-R1.40 and 129S1-R1.40 mice do not develop amyloid beta deposits in the parietal or frontal cortex even by 20 months of age. The donating investigator further reports that the A-R1.40 strain exhibits levels of amyloid beta comparable to the B6-R1.40 strain, but with later onset. Therefore, APP processing and amyloid beta metabolism and deposition are modified by the genetic background. While the 129S1-R1.40 strain can be easily maintained as homozygotes, the donating investigator reports increased mortality in young homozygotes on the other genetic backgrounds, with D2-R1.40 and A-R1.40 more severely affected than B6-R1.40.
Hemizygous: Hemizygous transgenic phenotype is expected to be similar to homozygote phenotype.

MeSH Terms
  • Alzheimer Disease/genetics
  • Amyloid beta-Protein Precursor/genetics
  • Amyloid beta-Protein Precursor/metabolism
  • Animals
  • Cell Culture Techniques
  • Chromosomes, Artificial, Yeast
  • Gene Expression
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Transgenic/genetics
  • Mutagenesis
  • Polymerase Chain Reaction
  • RNA, Messenger/metabolism
  • Transgenes/genetics
Strain 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 APPK670N/M671L associated with Familial Alzheimer's Disease. This transgene was injected into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Founder animals (line R1.40) were backcrossed to C57BL/6J for 21 generations prior to arrival at The Repository.
Suggested Control Mice
Wild-ype littermates
  • Models for Human Disease
  • Neurobiology
Donor
Bruce Lamb, Ph.D., The Cleveland Clinic Foundation
Primary Reference
Lamb BT, Call LM, Slunt HH, Bardel KA, Lawler AM, Eckman CB, Younkin SG, Holtz G, Wagner SL, Price DL, Sisodia SS, Gearhart JD. Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet. 1997 Sep;6(9):1535-41. (Medline PMID: 9285791)

Colony and Husbandry Informationon

When maintaining a live colony, transgenic carriers may be bred together, to wildtype siblings, or to C57BL/6J inbred mice. Because of the increased mortality in young homozygous animals (higher incidence in females), maintaining the colony by breeding homozygotes together is only recommended when sufficient colony size is permitted.
Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org .

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

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 $) Units Notes
034831-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity2
034831-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter1; additional fees for any special requests.

1 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.

2 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.

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

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.