Strain Name:
STOCK Nos2+ Tg(APPSWE)2576Kha Tg(Thy1-PSEN1*A246E)16-3Sqn/Mmnc
Stock Number:
011170-UNC
Citation ID:
RRID:MMRRC_011170-UNC
Other Names:
B6;SJL-Nos2+ Tg(APPSWE)2576Kha Tg(PSEN1)1Zhe/Mmnc
Alternate allele names: Tg(Prnp-APP*K670N,M671L)2576Kha and Tg(THY1-PSEN1*A246E)16-3Sqn

Gene Information

Nos2+
Name: nitric oxide synthase 2, inducible; wild type
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 11
Alteration at locus: Non-mutant
Nos2
Name: nitric oxide synthase 2, inducible
Synonyms: NOS-II, Nos2a, iNOS, Nos-2
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 11
Alteration at locus: Non-mutant
NCBI: 18126
HGNC: HGNC:7873
Homologene: 55473
Tg(APPSWE)2576Kha
Name: transgene insertion 2576, Karen Hsiao Ashe
Synonyms: APPSw, Tg(HuAPP695.K670-M671L)2576, K670N/M671L, APPswe Tg2576, TgN(APPSWE)2576, APP695swe, Tg(APPSWE)2576Kahs, Tg(APPSWE)2576HKahs, APPK670N,M671L, hAPP, Tg2576
Type: Allele
Species: Multi-species
Chromosome: unknown
Alteration at locus: Transgenic
Tg(Thy1-PSEN1*A246E)16-3Sqn
Name: transgene insertion 16-3, Su Qian
Type: Allele
Species: Homo sapiens (human)
Chromosome: unknown
Alteration at locus: Transgenic
PSEN1
Name: presenilin 1 (Alzheimer disease 3)
Type: Gene
Species: Homo sapiens (human)
Chromosome: 14
Alteration at locus: Transgenic
THY1
Name: Thy-1 cell surface antigen
Type: Gene
Species: Homo sapiens (human)
Chromosome: 11
Alteration at locus: Transgenic
APP
Name: amyloid beta precursor protein
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Alteration at locus: Transgenic
Prnp
Name: prion protein
Type: Gene
Species: Mesocricetus auratus (golden hamster)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations

For the nitric oxide synthase (Nos2) knockout, 585 bp of the promoter and exons 1-4 were deleted while inserting a neo cassette (PMID:7538909). Two additional transgenes were brought together with the KO, where (A) the gold hamster prion protein (Prnp) promoter drives the expression of human amyloid beta (A4) precursor protein (APP, NCBI Gene:351) with the Swedish mutation (K670N/M671L), and (B) the human thymus cell antigen 1, theta (THY1, NCBI Gene:7070) promoter drives the expression of human presenilin 1 (PSEN1, NCBI Gene:5663) with the A246E mutation. In this particular strain, the KO allele is not present through coordinated interbreeding (i.e., wild-type).

HGVS nomenclature:
  • PSEN1 A246E mutation
    • Genbank RefSeq - mRNA: NM_000021.4
    • Genbank RefSeq, protein: NP_000012.1
    • Variant, nucleic acid level: c.737C>A
    • Variant, amino acid level, predicted: p.Ala246Glu
      Check this variant: LUMC Mutalyzer

  • APP "Swedish Mutation" - K670N/M671L
    • Genbank RefSeq - mRNA: NM_001198823.1
    • Genbank RefSeq, protein: NP_001185752.1
    • Variant, nucleic acid level: c.2010G>T and c.2011A>C = c.2010_2011inv
    • Variant, amino acid level, predicted: p.Lys670_Met671delinsAsnLeu (K670N/M671L)
      Check this variant: LUMC Mutalyzer
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    AB2.1 derived from 129S7/SvEvBrd-Hprtb-m2
    Phenotype
    Alzheimer's disease-like brain pathology and premature mortality
    Mammalian Phenotype Terms
    Allelic Composition: Tg(APPSWE)2576Kha/Tg(APPSWE)2576Kha (Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL )

    Allelic Composition: Tg(APPSWE)2576Kha/0 (Genetic Background: FVB.Cg-Tg(APPSWE)2576Kha )

    Allelic Composition: Tg(APPSWE)2576Kha/0 (Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL )

    Allelic Composition: Tg(APPSWE)2576Kha/0 (Genetic Background: involves: C57BL/6 * DBA/2 * SJL * SW )

    Allelic Composition: Tg(APPSWE)2576Kha/0 (Genetic Background: involves: C57BL/6 * SJL )

    Allelic Composition: Tg(APPSWE)2576Kha/0 (Genetic Background: involves: C57BL/6J * SJL )

    MeSH Terms
    • Alzheimer Disease/enzymology
    • Alzheimer Disease/genetics
    • Alzheimer Disease/mortality
    • Alzheimer Disease/pathology
    • Animals
    • Brain/enzymology
    • Brain/pathology
    • Crosses, Genetic
    • Disease Models, Animal
    • Gene Deletion
    • Humans
    • Inbreeding
    • Mice
    • Mice, Inbred C57BL
    • Mice, Knockout
    • Mice, Transgenic
    • Nitric Oxide Synthase Type II/deficiency
    • Nitric Oxide Synthase Type II/genetics
    • Aging
    • Alzheimer Disease/metabolism
    • Amyloid beta-Peptides/analysis
    • Amyloid beta-Protein Precursor/analysis
    • Amyloid beta-Protein Precursor/genetics
    • Brain Chemistry
    • Learning Disabilities/metabolism
    • Learning Disabilities/pathology
    • Maze Learning
    • Memory Disorders/metabolism
    • Memory Disorders/pathology
    • Peptide Fragments/analysis
    • Psychomotor Performance
    • Amino Acid Oxidoreductases/deficiency
    • Amino Acid Oxidoreductases/genetics
    • Bacterial Infections/metabolism
    • Base Sequence
    • Mice, Mutant Strains
    • Molecular Sequence Data
    • Nitric Oxide Synthase
    • Shock, Septic/metabolism
    • Amyloid beta-Protein Precursor/metabolism
    • Astrocytes/metabolism
    • Astrocytes/pathology
    • Blotting, Western
    • Cerebral Cortex/metabolism
    • Cerebral Cortex/pathology
    • Cerebral Cortex/ultrastructure
    • Female
    • Glial Fibrillary Acidic Protein/metabolism
    • Immunohistochemistry
    • Microscopy, Confocal
    • Neurons/metabolism
    • Neurons/pathology
    • Neurons/ultrastructure
    • Nitric Oxide/metabolism
    • Nitric Oxide Synthase/metabolism
    • Plaque, Amyloid/metabolism
    • Plaque, Amyloid/pathology
    • Tyrosine/analogs & derivatives
    • Tyrosine/metabolism
    • Bone and Bones/abnormalities
    • Bone and Bones/embryology
    • Brain/abnormalities
    • Brain/embryology
    • Brain Chemistry/genetics
    • Gene Expression Regulation, Developmental/physiology
    • Male
    • Membrane Proteins/genetics
    • Mutagenesis/physiology
    • Pregnancy
    • Presenilin-1
    • Transgenes/physiology
    • Amino Acid Sequence
    • Codon/genetics
    • Exons
    • Genetic Linkage
    • Genetic Variation
    • Middle Aged
    • Oligodeoxyribonucleotides
    • Pedigree
    • Point Mutation
    • Transcription, Genetic
    • Alzheimer Disease
    • Behavior, Animal
    • Brain/metabolism
    • Central Nervous System Diseases/genetics
    • Central Nervous System Diseases/mortality
    • Central Nervous System Diseases/physiopathology
    • Cosmids
    • Gene Expression
    • Genetic Vectors
    • Glucose/metabolism
    Strain Development
    First, the donor backcrossed the original inducible nitric oxide synthase 2 knockout mice ("iNOS", Nos2 - MGI:97361, C57BL/6;129S7 - PMID:7538909) to C57BL/6 for six generations. Descendants of brother-sister matings were crossed with the SJL strain, and their progeny were interbred to derive a mix of B6/SJL/129S7 mice (officially STOCK designation since genetic components of >2 inbred lines are present without further backcrossing to congenicity). This step was based on evidence that that modifier genes from the SJL background were critical to avoid premature mortality in C57BL/6 mice bearing a mutant (K670N, M671L) human APP transgene ("hAPP", PMID:8810256). The B6/SJL/129S7 mice were mated with "Tg2576" mice, in which the hamster prion promoter drives the K670N/M671L APP transgene in the B6;SJL background (PMID:15450355 and 8810256), and with transgenics in which the human THY1 promoter drives human presenilin 1 ("hPS1", PSEN1) with the A246E mutation in the B6;SJL background (PMID:9539133). The donor interbred the progeny to establish three sublines from littermates:

    1. wild-type mice (iNOS+/+/hAPP0/0/hPS10/0) - MMRRC:11169
    2. mice with wild-type iNOS alleles and the APP and PS1 transgenes, each of which was inherited from only one parent so as to avoid overdose (iNOS+/+/hAPP+/0/hPS1+/0) - MMRRC:11170
    3. mice with disrupted iNOS alleles and the APP and PS1 transgenes (iNOS-/-/hAPP+/0/hPS1+/0) - MMRRC:11171
    Suggested Control Mice

    Wild-type littermates - MMRRC:11169

    • Immunology and Inflammation
    • Models for Human Disease
    Donor
    Carl Nathan, M.D., Weill Cornell Medical College.
    Hui Zheng, Ph.D., Baylor College of Medicine, Huffington Center on Aging.
    Karen Hsiao Ashe, M.D., University of Minnesota.
    Primary Reference

    Nathan C, Calingasan N, Nezezon J, Ding A, Lucia MS, La Perle K, Fuortes M, Lin M, Ehrt S, Kwon NS, Chen J, Vodovotz Y, Kipiani K, Beal MF. Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. J Exp Med. 2005 Nov 7;202(9):1163-9. Epub 2005 Oct 31. (Medline PMID: 16260491)

    Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996 Oct 4;274(5284):99-102. (Medline PMID: 8810256)

    MacMicking JD, Nathan C, Hom G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N, et al. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell. 1995 May 19;81(4):641-50. Erratum in: Cell 1995 Jun 30;81(7):following 1170. (Medline PMID: 7538909)

    Rodrigo J, Fernández-Vizarra P, Castro-Blanco S, Bentura ML, Nieto M, Gómez-Isla T, Martínez-Murillo R, MartInez A, Serrano J, Fernández AP. Nitric oxide in the cerebral cortex of amyloid-precursor protein (SW) Tg2576 transgenic mice. Neuroscience. 2004;128(1):73-89. (Medline PMID: 15450355)

    Qian S, Jiang P, Guan XM, Singh G, Trumbauer ME, Yu H, Chen HY, Van de Ploeg LH, Zheng H. Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates Abeta1-42/43 expression. Neuron. 1998 Mar;20(3):611-7. (Medline PMID: 9539133)

    Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, Lannfelt L. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet. 1992 Aug;1(5):345-7. (Medline PMID: 1302033)

    Hsiao KK, Borchelt DR, Olson K, Johannsdottir R, Kitt C, Yunis W, Xu S, Eckman C, Younkin S, Price D, et al. Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron. 1995 Nov;15(5):1203-18. (Medline PMID: 7576662))

    Colony and Husbandry Information

    MMRRC Breeding System
    Sib-mating
    Overall Breeding Performance
    Good
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Yes Yes
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: >12 months >12 months
    Bred to Homozygosity
    No
    Average litter size
    5
    Recommended wean age
    3 weeks
    Average Pups Weaned
    5

    Order Request Information

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

    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.edu for more information.

    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.

    - Products for this strain are Not Yet Available for Ordering
    - If you register interest in this strain, you will be notified when it becomes available for ordering.

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