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 A&beta;PP] 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 (A&beta;) peptides that cannot be transported out of the brain across the cerebrovascular interface and results in A&beta; peptide accumulation at the blood vessels (see C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax). The Nos2 mutation results in loss of inducible NOS (iNOS) expression which alters physiological functions related to disease and injury (see B6.129P2-Nos2tm1Lau/J). Homozygous bigenic mice (APPSwDI/NOS2-/-) progress from Abeta; 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.

These APPSwDI/NOS2 bigenic mice harbor the APPSwDI transgene and a targeted "null" mutation of the nitric oxide synthase 2 (Nos2) locus. Homozygous bigenic mice (APPSwDI/NOS2-/-) progress from A&beta; 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. These APPSwDI/NOS2 bigenic mice may be useful in studying Alzheimer's disease progression and the role of nitric oxide in altering chronic neurological disease processes.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.