A challenge with GRN mice was that homozygous and heterozygous GRN knockout mice failed to clearly present human FTD-like phenotypes, since heterozygous GRN knockout (GRN+/−) generally showed a low degree of neuropathology, while homozygous GRN knockout mice displayed more severe phenotypes, which were rarely observed in FTD patients. This evidence concerns the gene GRN and frontotemporal dementia.