Strain Detail Sheet

Strain Name:
B6.Cg-Nfatc2tm1Rao Tg(APPswe,PSEN1dE9)85Dbo/Mmmh
Stock Number:
041200-MU
Citation ID:
RRID:MMRRC_041200-MU
Other Names:
APP/PS1xNFATc2-/-

Strain Information

Gene Details

Nfatc2tm1Rao
Name: nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2; targeted mutation 1, Anjana Rao
Synonyms: NFATC2-, NFAT1-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 2
Alteration at locus: Knockout
Nfatc2
Name: nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2
Synonyms: NFAT1-D, NFATp, NFAT1
Type: Gene
Species: Mouse
Chromosome: 2
Alteration at locus: Knockout
NCBI: 18019
HGNC: HGNC:7776
Homologene: 7861
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PSEN1
Name: presenilin 1 (Alzheimer disease 3)
Type: Gene
Species: Homo sapiens (human)
Chromosome: 14
Alteration at locus: Knockout
APPswe
Name: amyloid beta (A4) precursor protein 695 (swedish mutation)
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Alteration at locus: Knockout
APP
Name: amyloid beta precursor protein
Type: Gene
Species: Homo sapiens (human)
Chromosome: 21
Alteration at locus: Knockout
Tg(APPswe,PSEN1dE9)85Dbo
Name: transgene insertion 85, David R Borchelt
Synonyms: APPswe/PS1dE9, APdE9, APPswe/PS1deltaE9, 2xTg Ad, APP-PS1, APP/PS1, Mo/Hu APPswe PS1dE9
Type: Transgene
Species: Mus musculus (mouse)
Chromosome: unknown
Alteration at locus: Transgenic
Genetic Alterations

Tg(APPswe,PSEN1dE9)85Dbo: Two expression plasmids (Mo/HuAPP695swe and PS1-dE9) were designed to each be controlled by independent mouse prion protein (PrP) promoter elements, directing transgene expression predominantly to CNS neurons. The Mo/HuAPP695swe transgene expresses a humanized mouse amyloid beta (A4) precursor protein gene, modified at three amino acids to reflect the human residues and further modified to contain the K595N/M596L (otherwise known as K670N/M671L) mutations linked to familial Alzheimers. The PS1-dE9 transgene expresses a mutant human presenilin 1 carrying the exon-9-deleted variant (PSEN1dE9) associated with familial Alzheimer.

Nfatc2tm1Rao: A neo cassette was inserted into an exon encoding amino acids near amino-terminus of the DNA binding domain.

Genotype Determination
ES Cell Line
Not specified

Strain Description

Phenotype

Note: The mice are homozygous for the NFATc2 knockout but heterozygous for the APP/PS1 genes since homozygous APP/PS1 mice do not survive.

These mice still deposit robust Abeta peptide containing plaques in the brain but do not have the characteristic reactive microglial or astrocyte activation associated with plaque deposition.

Mammalian Phenotype Terms
Allelic Composition: Nfatc2tm1Rao/Nfatc2tm1Rao (Genetic Background: B6.Cg-Nfatc2tm1Rao )
MeSH Terms
  • Alzheimer Disease/metabolism
  • Alzheimer Disease/pathology
  • Amyloid beta-Protein Precursor/genetics
  • Amyloid beta-Protein Precursor/metabolism
  • Animals
  • Brain/metabolism
  • Brain/pathology
  • Cell Line
  • Cells, Cultured
  • Cytokines/metabolism
  • Disease Models, Animal
  • Gliosis/metabolism
  • Gliosis/pathology
  • Humans
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia/metabolism
  • Microglia/pathology
  • NFATC Transcription Factors/antagonists & inhibitors
  • NFATC Transcription Factors/genetics
  • NFATC Transcription Factors/metabolism
  • Plaque, Amyloid/metabolism
  • Plaque, Amyloid/pathology
  • Presenilin-1/genetics
  • Presenilin-1/metabolism
  • RNA, Messenger/metabolism
Strain Development

NFATc2KO (Nfatc2tm1Rao) sibling females (MMRRC:197) were bred to multiple non-sibling APP/PS1 (B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax - JAX Strain #005864) males. The F1 offspring heterozygous for both traits were then bred to each other to produce F2 mice homozygous for Nfatc2tm1Rao and hemizygous for the transgene.

Suggested Control Mice
Wild-type littermates

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 mmrrc@missouri.edu. Older strains may not have this information.

Research Applications

  • Immunology and Inflammation
  • Neurobiology

Strain Origin

Donor
Colin Combs, Ph.D., University of North Dakota.
Anjana Rao, Ph.D., La Jolla Institute.
David Borchelt, Ph.D., University of Florida.
Primary Reference

Manocha GD, Ghatak A, Puig KL, Kraner SD, Norris CM, Combs CK. NFATc2Modulates Microglial Activation in the AβPP/PS1 Mouse Model of Alzheimer'sDisease. J Alzheimers Dis. 2017;58(3):775-787. doi: 10.3233/JAD-151203. (Medline PMID: 28505967)

Colony and Husbandry Information

Health Status Report

Colony Surveillance Program and Current Health Reports

For more information about this colony's health status contact mmrrc@missouri.edu

Appearance

Coat Color
Black or agouti

Breeding

MMRRC Breeding System
Sib-mating
Breeding Scheme(s)
Hemizygous (transgene) male x Wild-type (transgene) female littermate

Note: All mice are homozygous for the Nfatc2tm1Rao allele

Generation
F8
Overall Breeding Performance
Good

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: Yes Yes
Homozygotes are fertile: Yes Yes
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Bred to Homozygosity
Yes
Average litter size
4-6
Recommended wean age
3-4 weeks
Average Pups Weaned
4-6

Order Request Information

Availability Level

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@missouri.edu for more information.

Conditions of Distribution

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

- 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.
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.