Allele Symbol: Nos2tm1Lau
Name: targeted mutation 1, Victor E Laubach
Alteration at locus: Targeted Mutation
Gene Symbol: Nos2
Name: nitric oxide synthase 2, inducible
Alteration at locus: Targeted Mutation
Name: transgene insertion B, William E Van Nostrand
Alteration at locus: Transgenic
ES Cell Line: E14TG2a
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.
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
Donor: William Van Nostrand, Ph.D., Stony Brook University
When maintaining a live colony, mice homozygous for the targeted mutation and homozygous for the transgene may be bred together.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Fee/unit (US $)
|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.