Progranulin insufficiency and TDP-43 overexpression interact to worsen FTD-related phenotypes in mice.

Progranulin (GRN) mutations, which typically cause progranulin haploinsufficiency, cause frontotemporal dementia with TDP-43 pathology (FTD-TDP). It is not clear how progranulin insufficiency may cause FTD-TDP. Progranulin-insufficient mice develop FTD-related phenotypes without robust TDP-43 pathology, so we crossed crossed Grn+/- mice (RRID:MMRRC_036771-JAX) with transgenic mice expressing wild-type human TDP-43 (RRID:IMSR_JAX:012836) to investigate the effect of progranulin insufficiency on TDP-43 aggregation and TDP-43–related phenotypes.