Species: Mouse
Genes: BACE1
Modification: BACE1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: C57BL/6 J
Availability: Available through Material Transfer Management at Novartis

Summary

These mice were generated to determine how BACE overexpression affects the processing of APP in vivo. Two transgenic lines were reported (BACE54/4 and BACE54/11) both expressing human BACE at high levels in the brain. Human BACE mRNA was approximately 4-fold higher than endogenous murine BACE mRNA. The highest expression of human BACE protein was measured in the cortex and hippocampus, with lower levels in the cerebellum. The transgenic animals had significantly reduced levels of full-length APP and increased levels of C99 and C89, the proteolytic products generated by β-secretase cleavage. Neuropathology was not observed, and behavior was not assessed.

These mice have been crossed to mice overexpressing APP, such as the huAPP751 line (wild-type or carrying the Swedish mutation). Bigenic animals showed significant reduction of full-length APP, as well as elevated C99, C89 and sAPPβ, Aβ40 and Aβ42 (Bodendorf et al., 2002).

Modification Details

Wild-type human BACE driven by the murine Thy1 promoter.

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References

Paper Citations

1. Bodendorf U, Danner S, Fischer F, Stefani M, Sturchler-Pierrat C, Wiederhold KH, Staufenbiel M, Paganetti P. Expression of human beta-secretase in the mouse brain increases the steady-state level of beta-amyloid. J Neurochem. 2002 Mar;80(5):799-806. PubMed.

Further Reading