Modification: BACE1: Knock-Out
Disease Relevance: Alzheimer's Disease
Strain Name: B6.129-Bace1tm1Pcw/J
Genetic Background: C57BL/6J
Availability: The Jackson Lab: Stock# 004714; Live
These mice have a targeted deletion in the mouse gene β-site APP cleaving enzyme 1 (BACE1). Homozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. No BACE1 protein is detected by Western blot of brain tissue. Primary cultures of cortical neurons do not secrete Aβ1-40/42, Aβ11-40/42 or β-C terminal fragments (β-CTFs) (Cai et al., 2001). Hypomyelination was observed at post-natal days 15 and 30, but axonal development appeared normal. Decreased grip strength and increased sensitivity to a thermal stimulus as measured by latency to retract paws from a hot plate have also been reported (Hu et al., 2006).
Homologous recombination was used to disrupt a 2 kb section of BACE1 containing exon 1 replacing it with a neomycin selection cassette and the HSV thymidine kinse gene.
- Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL, Wong PC. BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat Neurosci. 2001 Mar;4(3):233-4. PubMed.
- Hu X, Hicks CW, He W, Wong P, Macklin WB, Trapp BD, Yan R. Bace1 modulates myelination in the central and peripheral nervous system. Nat Neurosci. 2006 Dec;9(12):1520-5. Epub 2006 Nov 12 PubMed.
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