Models of tauopathy

A non-human animal comprising:

• (a) a microtubule-associated protein tau coding sequence in one or more cells;
• and
• (b) (i) a genetic modification in one or more or all of BANF1, PPP2CA, and ANKLE2 that reduces expression of the one or more or all of BANF1, PPP2CA, and ANKLE2, respectively, in the one or more cells and/or (ii) one or more agents that reduce expression of one or more or all of BANF1, PPP2CA, and ANKLE2 in the one or more cells,
• wherein the microtubule-associated protein tau coding sequence is an exogenous human microtubule-associated protein tau coding sequence and/or wherein the microtubule-associated protein tau comprises a tauopathy-associated mutation.