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BACE1 across species: a comparison of the in vivo consequences of BACE1 deletion in mice and rats.

Authors: Weber, Martin  Wu, Tiffany  Meilandt, William J  Dominguez, Sara L  Solanoy, Hilda O  Maloney, Janice A  Ngu, Hai  Baca, Miriam  Kung, Chung  Lima, Lisa  Earr, Timothy K  Fleck, Daniel  Shields, Shannon D  Forrest, William F  Foreman, Oded  Warming, Søren  Watts, Ryan J  Scearce-Levie, Kimberly 
Citation: Weber M, etal., Sci Rep. 2017 Mar 10;7:44249. doi: 10.1038/srep44249.
Pubmed: (View Article at PubMed) PMID:28281673
DOI: Full-text: DOI:10.1038/srep44249

Assessing BACE1 (ß-site APP cleaving enzyme 1) knockout mice for general health and neurological function may be useful in predicting risks associated with prolonged pharmacological BACE1 inhibition, a treatment approach currently being developed for Alzheimer's disease. To determine whether BACE1 deletion-associated effects in mice generalize to another species, we developed a novel Bace1-/- rat line using zinc-finger nuclease technology and compared Bace1-/- mice and rats with their Bace1+/+ counterparts. Lack of BACE1 was confirmed in Bace1-/- animals from both species. Removal of BACE1 affected startle magnitude, balance beam performance, pain response, and nerve myelination in both species. While both mice and rats lacking BACE1 have shown increased mortality, the increase was smaller and restricted to early developmental stages for rats. Bace1-/- mice and rats further differed in body weight, spontaneous locomotor activity, and prepulse inhibition of startle. While the effects of species and genetic background on these phenotypes remain difficult to distinguish, our findings suggest that BACE1's role in myelination and some sensorimotor functions is consistent between mice and rats and may be conserved in other species. Other phenotypes differ between these models, suggesting that some effects of BACE1 inhibition vary with the biological context (e.g. species or background strain).

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RGD Object Information
RGD ID: 13782149
Created: 2018-08-23
Species: All species
Last Modified: 2018-08-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.