Grn^tm1.1Hiok

A mutation was introduced into BAC RP23-311P1 that changes arginine codon 504 (AGG) to a stop codon (p.R504*). This mutation corresponds to the human p.R493* mutation causally linked to PGRN-linked frontotemporal lobar degeneration (FTLD). This BAC was used to create a targeting vector, and homologous recombination in ES cells and production of chimeric mice transmitted the mutation into the mouse germline. A loxP site flanked neomycin selection cassette was removed by Cre-mediated recombination in mice. Western blot analysis shows that level of full-length protein is reduced in the cerebral cortex (J:259943)