Species: Mouse
Genes: APP
Mutations: APP E693Q (Dutch)
Modification: APP: Transgenic
Disease Relevance: Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease
Strain Name: C57BL/6J-Tg(Thy1-APPDutch)#Jckr
Genetic Background: C57BL/6J
Availability: Available through Mathias Jucker

Summary

This transgenic mouse line bears a mutation that was determined to cause hereditary cerebral hemorrhage with amyloidosis-Dutch type, a rare autosomal dominant disorder characterized by cerebral amyloid angiopathy (CAA), strokes, and dementia. APPDutch mice have an increased Aβ40/Aβ42 ratio, but parenchymal amyloid plaques are not observed. Instead, mice develop extensive vascular Aβ deposition starting at 22 to 24 months of age, and appearing first in leptomeningeal vessels followed by cortical vessels. This leads to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. The mice develop robust microgliosis immediately adjacent to amyloid-laden vessels, and widespread activation of astrocytes in neocortical regions affected by CAA. Female mice have earlier onset of amyloid deposition (Herzig et al., 2004).

Modification Details

Transgenic mice with human APP751 bearing the E693Q mutation under the murine Thy1 promoter.

The parental origin of the transgenes was shown to influence AD-related pathology in another model, 5xFAD (C57BL6), in which the Thy1 promoter drives transgene expression, possibly due to genomic imprinting of the promoter (Sasmita et al.,  2025). While this phenomenon has not yet been demonstrated in APP Dutch mice, users of this model should be aware of the findings in 5xFAD mice when designing and documenting breeding strategies.

Phenotype Characterization

COMMENTS / QUESTIONS

1. • Takaomi Saido
     RIKEN Center for Brain Science
   • Posted: 26 Aug 2004
   • Paper: Abeta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis.

   The work provides insights into the significance of conformational versus metabolic properties in the occurrence of pathological phenotypes, i.e., amyloid angiopathy versus parenchymal amyloidosis.

   View all comments by Takaomi Saido

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References

Research Models Citations

1. 5xFAD (C57BL6)

Paper Citations

1. Herzig MC, Winkler DT, Burgermeister P, Pfeifer M, Kohler E, Schmidt SD, Danner S, Abramowski D, Stürchler-Pierrat C, Bürki K, van Duinen SG, Maat-Schieman ML, Staufenbiel M, Mathews PM, Jucker M. Abeta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis. Nat Neurosci. 2004 Sep;7(9):954-60. PubMed.
2. Sasmita AO, Ong EC, Nazarenko T, Mao S, Komarek L, Thalmann M, Hantakova V, Spieth L, Berghoff SA, Barr HJ, Hingerl M, Börensen F, Hirrlinger J, Simons M, Stevens B, Depp C, Nave KA. Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease. Neuron. 2025 Jan 20; Epub 2025 Jan 20 PubMed.

Other Citations

1. Mathias Jucker

Further Reading