A rodent, an animal tissue, or a population of animal cells comprising: (a) an exogenous human microtubule-associated protein tau coding sequence in a plurality of cells, wherein the exogenous human microtubule-associated protein tau comprises a tauopathy-associated mutation, wherein the exogenous human microtubule-associated protein tau coding sequence is expressed in the plurality of cells, and wherein the plurality of cells are neuronal cells; and (b) (i) a genetic modification in one or both of BANF1 and ANKLE2 that reduces expression of the one or both of BANF1 and ANKLE2, respectively, in the plurality of cells compared to a plurality of cells without the genetic modification and/or (ii) one or more agents that reduce expression of one or both of BANF1 and ANKLE2 in the plurality of cells compared to a plurality of cells without the one or more agents, and wherein at least one sign or symptom of tauopathy is increased in the rodent, the animal tissue or the population of animal cells relative to a rodent, an animal tissue, or a population of animal cells that does not comprise the genetic modification in the one or both of BANF1 and ANKLE2 or does not comprise the one or more agents that reduce expression of one or both of BANF1 and ANKLE2, wherein the at least one sign or symptom comprises: (I) tau hyperphosphorylation or tau aggregation; and/or (II) increased tau and/or phospho-tau in an insoluble fraction following cell fractionation, increased phospho-tau in the somatodendritic compartment of neurons, increased phospho-tau in the perinuclear region of neurons, decreased nuclear pore complex protein Nup98-Nup96 (Nup98) nuclear-to-cytoplasmic ratio in neurons, decreased GTP-binding nuclear protein Ran (Ran) nuclear-to-cytoplasmic ratio in neurons, or decreased Ran GTPase-activating protein 1 (RanGAP1) nuclear-to-cytoplasmic ratio in neurons. (a) an exogenous human microtubule-associated protein tau coding sequence in a plurality of cells, wherein the exogenous human microtubule-associated protein tau comprises a tauopathy-associated mutation, wherein the exogenous human microtubule-associated protein tau coding sequence is expressed in the plurality of cells, and wherein the plurality of cells are neuronal cells; and wherein the exogenous human microtubule-associated protein tau comprises a tauopathy-associated mutation, wherein the exogenous human microtubule-associated protein tau coding sequence is expressed in the plurality of cells, and wherein the plurality of cells are neuronal cells; and (b) (i) a genetic modification in one or both of BANF1 and ANKLE2 that reduces expression of the one or both of BANF1 and ANKLE2, respectively, in the plurality of cells compared to a plurality of cells without the genetic modification and/or (ii) one or more agents that reduce expression of one or both of BANF1 and ANKLE2 in the plurality of cells compared to a plurality of cells without the one or more agents, and (I) tau hyperphosphorylation or tau aggregation; and/or (II) increased tau and/or phospho-tau in an insoluble fraction following cell fractionation, increased phospho-tau in the somatodendritic compartment of neurons, increased phospho-tau in the perinuclear region of neurons, decreased nuclear pore complex protein Nup98-Nup96 (Nup98) nuclear-to-cytoplasmic ratio in neurons, decreased GTP-binding nuclear protein Ran (Ran) nuclear-to-cytoplasmic ratio in neurons, or decreased Ran GTPase-activating protein 1 (RanGAP1) nuclear-to-cytoplasmic ratio in neurons. <EOS>