Generation of a New Tau Knockout (tau^Δex1) Line Using CRISPR/Cas9 Genome Editing in Mice

Article type: Short Communication

Authors: Tan, Daniel C.S.^{a; b} | Yao, Sherilyn^b | Ittner, Arne^a | Bertz, Josefine^a | Ke, Yazi D.^c | Ittner, Lars M.^{a; b; d; *} | Delerue, Fabien^b

Affiliations: [a] Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia | [b] Transgenic Animal Unit, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia | [c] Motor Neuron Disease Unit, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia | [d] Neuroscience Research Australia, Sydney, NSW, Australia

Correspondence: [*] Correspondence to: Lars M. Ittner, Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney 2052, NSW, Australia. E-mail: l.ittner@unsw.edu.au.

Abstract: Alzheimer’s disease and other dementias present with tau pathology. Several mouse lines with knockout of the tau-encoding Mapt gene have been reported, yet findings often differed between lines and sites. Here, we report a new tau knockout strain (tauΔex1), generated by CRISPR/Cas9-mediated genome editing of intron -1/exon 1 of Mapt in C57Bl/6J mice. TauΔex1 mice had no overt phenotype, but, in line with previous models, they showed a significantly reduced susceptibility to excitotoxic seizures, with normal memory formation in young mice. This new in vivo resource will be made freely available to the research community.

Keywords: C57Bl/6, CRISPR, gene knockout, mouse, tau

DOI: 10.3233/JAD-171058

Journal: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 571-578, 2018