Strain Detail Sheet

Strain Name    :

B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax

Stock Number :

034849-JAX

Other Names   :

This strain was formerly available as JaxMice stock number 9126. APPSwDI/NOS2 bigenic mice, APPSwDI/NOS2-/-

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Nos2tm1Lau
Name: targeted mutation 1, Victor E Laubach
Alteration at locus: Targeted Mutation
Gene Symbol: Nos2
Name: nitric oxide synthase 2, inducible
Chromosome: 11
Alteration at locus: Targeted Mutation
Transgene: Tg(Thy1-APPSwDutIowa)BWevn
Name: transgene insertion B, William E Van Nostrand
Alteration at locus: Transgenic

Genetic Alterations:

Genotype Determination:

ES Cell Line: E14TG2a

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous phenotype: These APPSwDI/NOS2 bigenic mice harbor the APPSwDI transgene and a targeted "null" mutation of the nitric oxide synthase 2 (Nos2) locus. Expression of the APPSwDI transgene (a neuronally derived human amyloid beta-precursor protein [APP or AβPP] 770 isoform containing three Alzheimer's disease-associated mutations [Swedish K670N/M671L, Dutch E693Q and Iowa D694N] all under the control of the mouse thymus cell antigen 1, theta [Thy1] promoter) produces amyloid-beta (Aβ) peptides that cannot be transported out of the brain across the cerebrovascular interface and results in Aβ peptide accumulation at the blood vessels. The Nos2 mutation results in loss of inducible NOS (iNOS) expression which alters physiological functions related to disease and injury. Homozygous bigenic mice (APPSwDI/NOS2-/-) progress from Aβ production and amyloid deposition to hyperphosphorylated normal mouse tau at Alzheimer's disease-associated epitopes, aggregation and redistribution of tau to somatodendritic regions of neurons, significant neuronal loss (including loss of interneurons), moderate-severe cerebral amyloid angiopathy, and severe learning and memory deficits. This Alzheimer's disease-like pathology is also accompanied by robust behavioral changes. Compared to mice only harboring the APPSwDI transgene, these APPSwDI/NOS2 bigenic mice exhibit more severe human Alzheimer's disease pathology and additional human Alzheimer's disease features, and may be useful in studying Alzheimer's disease progression and the role of nitric oxide in altering chronic neurological disease processes.
Hemizygous transgenic phenotype: Hemizygote phenotype is expected to be similar to homozygote phenotype.
Heterozgous phenotype: Heterozygote phenotype is expected to be similar to the wild-type phenotype.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Nos2/Nos2 Tg(Thy1-APPSwDutIowa)BWevn/?
        involves: C57BL/6
  • nervous system phenotype
    • abnormal brain interneuron morphology (MGI Ref ID J:143551)
      • 65% loss of NPY interneurons in the hippocampus
    • abnormal hippocampus CA3 region morphology (MGI Ref ID J:143551)
      • neuronal loss
    • abnormal subiculum morphology (MGI Ref ID J:143551)
      • neuronal loss
    • amyloid beta deposits (MGI Ref ID J:143551)
      • deposits are observed by 52 weeks of age
    • decreased neuron number (MGI Ref ID J:143551)
      • neuronal loss is observed in hippocampus, subiculum and CA3
  • other phenotype
    • amyloid beta deposits (MGI Ref ID J:143551)
      • deposits are observed by 52 weeks of age

Strain of Origin: C57BL/6 and 129P2/OlaHsd

Strain genetic background: B6.Cg

Strain Development: To generate this double mutant colony, homozygous Tg(Thy1-APPSwDutIowa)BWevn females were bred with heterozygous or homozygous Nos2tm1Lau males. The resulting double mutant animals were bred together.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest at least one of the parental strains sent to Th Repository were on a C57BL/6N genetic background.

Suggested Control Mice: Wild-ype littermates

Research Applications

  • Models for Human Disease
  • Neurobiology

Strain Origin

Donor: William Van Nostrand, Ph.D., Stony Brook University

Primary Reference:

  • Davis J; Xu F; Deane R; Romanov G; Previti ML; Zeigler K; Zlokovic BV; Van Nostrand WE, Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor., J Biol Chem 2004 May 7;279(19):20296-306 (Medline PMID: 14985348)
  • Colton CA; Wilcock DM; Wink DA; Davis J; Van Nostrand WE; Vitek MP, The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP., J Alzheimers Dis 2008 Dec;15(4):571-87 (Medline PMID: 19096157)

Colony and Husbandry Information

Special Considerations

When maintaining a live colony, mice homozygous for the targeted mutation and homozygous for the transgene may be bred together.

Health Status Report

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

Availability Level

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

Conditions of Distribution [Including applicable technology transfer agreements]

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.

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 $)
Units Notes
034849-JAX-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
034849-JAX-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2

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 above). 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.



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.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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