Research Models

Tg-SwDI (APP-Swedish,Dutch,Iowa)

Synonyms: APPSwDI

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Species: Mouse
Genes: APP
Mutations: APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type
Strain Name: C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
Genetic Background: C57BL/6
Availability: The Jackson Lab; available through the JAX MMRRC Stock# 034843; Live

Neuropathology

The mice develop fibrillar amyloid deposits primarily in the cerebral microvasculature starting at approximately six months. Aβ deposition also occurs in the brain parenchyma, generally in the form of diffuse plaque-like structures which begin at approximately three months of age in the subiculum, hippocampus and cortex and spread to the olfactory bulb and thalamic regions by six months. Aβ deposits are detected throughout the forebrain by twelve months (Davis et al., 2004). The mice also develop gliosis with a pronounced increase in the number of GFAP-positive astrocytes and activated microglia at 6-24 months, especially in the thalamus and subiculum, and to a lesser extent in the cortex (Miao et al., 2005).

Cognition/Behavior

Learning and memory deficits have been detected in homozygotes at three, nine, and 12 months in the Barnes maze task. Beginning at three months, homozygotes took longer than wild-type C57BL/6 mice to find the escape hole. No differences in mobility, strength or coordination were reported (Xu et al., 2007).

Modification Details

These transgenic mice express the human APP gene (isoform 770) containing the Swedish (K670N/M671L), Dutch (E693Q), and Iowa (D694N) mutations under the control of the mouse Thy1 promoter.

Note

This model was previously available through The Jackson Lab as Stock# 007027.

Related Strains

This model was used to generate a double transgenic, APPSwDI/NOS2-/-, which has a more severe phenotype (Colton et al., 2008; Wilcock et al., 2008)

Phenotype Characterization

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

Absent

  • Tangles

No Data

  • Neuronal Loss
  • Synaptic Loss

Plaques

Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Amyloid-β deposits in the subiculum, hippocampus, and cortex at ~3 months. By ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (Davis et al., 2004).

Tangles

Absent.

Neuronal Loss

Unknown.

Gliosis

Pronounced increase in the number of GFAP-positive astrocytes and activated microglia with age (6-24 months) especially in the thalamus and subiculum and to a lesser extent in the cortex (Miao et al., 2005).

Synaptic Loss

Unknown.

Cognitive Impairment

Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months; beginning at 3 months took longer to find the escape hole. No difference in mobility, strength or coordination (Xu et al., 2007).

Last Updated: 25 Nov 2019

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References

Paper Citations

  1. Davis J, Xu F, Deane R, Romanov G, Previti ML, Zeigler K, Zlokovic BV, Van Nostrand WE. 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. Epub 2004 Feb 25 PubMed.
  2. Miao J, Xu F, Davis J, Otte-Höller I, Verbeek MM, Van Nostrand WE. Cerebral microvascular amyloid beta protein deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant amyloid beta precursor protein. Am J Pathol. 2005 Aug;167(2):505-15. PubMed.
  3. Xu F, Grande AM, Robinson JK, Previti ML, Vasek M, Davis J, Van Nostrand WE. Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid beta-protein precursor transgenic mice. Neuroscience. 2007 Apr 25;146(1):98-107. Epub 2007 Feb 28 PubMed.
  4. Colton CA, Wilcock DM, Wink DA, Davis J, Van Nostrand WE, Vitek MP. The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP. J Alzheimers Dis. 2008 Dec;15(4):571-87. PubMed.
  5. Wilcock DM, Lewis MR, Van Nostrand WE, Davis J, Previti ML, Gharkholonarehe N, Vitek MP, Colton CA. Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2. J Neurosci. 2008 Feb 13;28(7):1537-45. PubMed.

Other Citations

  1. APPSwDI/NOS2-/-

External Citations

  1. JAX MMRRC Stock# 034843

Further Reading

Papers

  1. Park L, Koizumi K, El Jamal S, Zhou P, Previti ML, Van Nostrand WE, Carlson G, Iadecola C. Age-dependent neurovascular dysfunction and damage in a mouse model of cerebral amyloid angiopathy. Stroke. 2014 Jun;45(6):1815-21. Epub 2014 Apr 29 PubMed.
  2. Xu F, Kotarba AE, Ou-Yang MH, Fu Z, Davis J, Smith SO, Van Nostrand WE. Early-onset formation of parenchymal plaque amyloid abrogates cerebral microvascular amyloid accumulation in transgenic mice. J Biol Chem. 2014 Jun 20;289(25):17895-908. Epub 2014 May 14 PubMed.
  3. Kruyer A, Soplop N, Strickland S, Norris EH. Chronic Hypertension Leads to Neurodegeneration in the TgSwDI Mouse Model of Alzheimer's Disease. Hypertension. 2015 Jul;66(1):175-82. Epub 2015 May 4 PubMed.