Modification: BACE2: Knock-Out
Disease Relevance: Alzheimer's Disease
Strain Name: B6;129P2-Bace2tm1Bdes/J
Genetic Background: Strain of origin: 129P2/OlaHsd
Availability: The Jackson Lab: Stock# 005618; Cryopreserved
These mice have a targeted deletion of part of the mouse β-site APP-cleaving enzyme 2 (BACE2) gene. In contrast to animals with targeted deletion of BACE1, homozygous BACE2 null animals are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No differences were detected in a standard battery of blood and clinical chemistry and no gross pathological differences have been observed by hematoxylin and eosin staining. Homozygous null animals lack BACE2 transcripts with exon 6. One of the enzyme's active sites is encoded by exon 6 and the resulting protein has been shown to lack protease activity (Dominguez et al., 2005).
Cre mediated recombination was used to remove exon 6 of BACE2. A targeting vector containing a loxP site and hygromycin resistance gene flanked by FRT sites was introduced into intron 5 and a second loxP site was inserted within intron 6. Heterozygous mice were crossed with mice expressing Cre under the ubiquitous phosphoglycerate kinase promoter to delete exon 6 in progeny.
- Dominguez D, Tournoy J, Hartmann D, Huth T, Cryns K, Deforce S, Serneels L, Camacho IE, Marjaux E, Craessaerts K, Roebroek AJ, Schwake M, D'Hooge R, Bach P, Kalinke U, Moechars D, Alzheimer C, Reiss K, Saftig P, De Strooper B. Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. J Biol Chem. 2005 Sep 2;280(35):30797-806. Epub 2005 Jun 29 PubMed.
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