Serial sections of spinal cord tissue from (a, d) 3.5, (b, e) 8.5 and (c, f) 10-month-old JNPL3 mice was immunostained for (a–c) TDP-43 phosphorylated at S409/410 and (d–f) tau phosphorylated at S202/T205 (AT8 antibody). JNPL3 mice at 3.5 months of age show (a) normal nuclear localization of pTDP-43 and (d) minimal tau pathology. (b) pTDP-43 remains localized in the neuronal nuclei as (e) tau pathology slowly accumulates in the spinal cord of 8.5-month-old JNPL3 lacking a motor phenotype. (c) Serial sectioning of a JNPL3 mouse with motor phenotype shows neurons with cytoplasmic relocalization of pTDP-43 (c, arrows) that also show prominent tau pathology (f, arrows). In addition, normal nuclear localization of pTDP-43 (c, asterisk) can be seen in cells with prominent tau pathology (f, asterisk). A healthy neuron without (c, square) cytoplasmic pTDP-43 or (f, square) tau pathology can also be seen. Robust cytoplasmic accumulation of phosphorylated TDP-43 in transgenic models of tauopathy: Clippinger AK, D'Alton S, Lin WL, Gendron TF, Howard J, Borchelt DR, Cannon A, Carlomagno Y, Chakrabarty P, Cook C, Golde TE, Levites Y, Ranum L, Schultheis PJ, Xu G, Petrucelli L, Sahara N, Dickson DW, Giasson B, Lewis J - Acta neuropathologica (2013). Not altered. CC.