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
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).
Wild-type human BACE driven by the murine Thy1 promoter.
- 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.
- Pastorino L, Ikin AF, Lamprianou S, Vacaresse N, Revelli JP, Platt K, Paganetti P, Mathews PM, Harroch S, Buxbaum JD. BACE (beta-secretase) modulates the processing of APLP2 in vivo. Mol Cell Neurosci. 2004 Apr;25(4):642-9. PubMed.
- Sala Frigerio C, Fadeeva JV, Minogue AM, Citron M, Van Leuven F, Staufenbiel M, Paganetti P, Selkoe DJ, Walsh DM. beta-Secretase cleavage is not required for generation of the intracellular C-terminal domain of the amyloid precursor family of proteins. FEBS J. 2010 Mar;277(6):1503-18. PubMed.