Research Models

APPSwDI/NOS2-/-

Synonyms: APPSwDI/NOS2 bigenic mice, APPSDI/NOS2KO, CVN

Tools

Back to the Top

Species: Mouse
Genes: APP, NOS2
Mutations: APP KM670/671NL (Swedish), APP E693Q (Dutch), APP D694N (Iowa)
Modification: APP: Transgenic; NOS2: Knock-Out;
Disease Relevance: Alzheimer's Disease
Strain Name: B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
Genetic Background: C57BL/6J; C57BL/6N
Availability: Jackson Labs: Stock# 009126; Cryopreserved. Charles River: CVN mouse

Modification Details

These bigenic mice harbor the APPSwDI transgene and a targeted null "mutation" of the nitric oxide synthase 2 (NOS2) locus. The APPSwDI transgene expresses APP (isoform 770) containing three mutations: Swedish K670N/M671L, Dutch E693Q, and Iowa D694N, under the control of the mouse Thy1 promoter.

Neuropathology

Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than APPSwDI alone.

Cognition/Behavior

Severe learning and memory deficits. Impaired spatial memory compared to APPSwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks.

Other Phenotypes

Decreased NPY staining throughout the hippocampus, particularly in the CA3 region and subiculum.

Note

Compared to mice only harboring the APPSwDI transgene, these bigenic mice exhibit more severe pathology. The phenotypes of the individual mice have been reported (Davis et al., 2004 and Laubach et al., 1995).
  

Phenotype Timeline

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Observed

Absent

Unknown

  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD

Plaques

Aβ deposits by 52 weeks. Particularly dense Aβ immunoreactivity in the subiculum and thalamus, including in the cerebral microvessels (Wilcock et al., 2008).

Tangles

Extensive tau pathology by 52 weeks, including intraneuronal aggregates of hyperphosphorylated tau. Increased phosphorylated tau in bigenic mice compared to APPSwDI mice (Wilcock et al., 2008).

Neuronal Loss

Significant neuron loss by 52 weeks in the hippocampus and subiculum, especially of neuropeptide Y neurons. Numerous Fluoro-Jade C+ neurons: 30% loss in the hippocampus, 35% loss in the subiculum (Wilcock et al., 2008).

Gliosis

Unknown.

Synaptic Loss

Unknown.

Changes in LTP/LTD

Unknown.

 

Cognitive Impairment

Impairments in spatial memory by 52-56 weeks as measured by the radial arm maze and the Barnes maze. Bigenic mice more impaired than APPSwDI (Wilcock et al., 2008).

COMMENTS / QUESTIONS

Make a comment or submit a question

To make a comment you must login or register.

Comments

No Available Comments

References

Paper Citations

  1. . 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. PubMed.
  2. . Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10688-92. PubMed.

Other Citations

  1. APPSwDI

External Citations

  1. Jackson Labs: Stock# 009126
  2. . Charles River: CVN mouse

Further Reading

No Available Further Reading