YAC128 mice were obtained from Jackson Labs (stock #4938) and maintained on the FVB-inbred background. These mice express full-length human huntingtin with 128 CAG repeats (hmHTT). Tails snips were obtained at 3 weeks of age and mice were genotyped by PCR as previously described (32 (link)). Male and female mice were used for experiments. Mice were maintained on a 12-hour light-dark cycle and were provided with access to cereal-based rodent chow (LabDiet®−6673) and water ad libitum. Each cage had a mouse igloo (Bio-Serv) and sani-chip bedding (Harlan Laboratories). Amyloid precursor protein (APP) global homozygous knockout mice were obtained from Jackson Labs (stock #4133). Dueto difficulties breeding APP mice were maintained on the hemizygous background. APP double knockout mice have been reported to demonstrate a phenotype characterized by elevated brain iron in response to dietary iron challenge, gliosis and impaired motor function (21 (link), 33 (link)). We are unaware of reports of effects of APP hemizygosity in these mice. Genotyping used a three-primer system: APP knockout forward: 5’ - AAG TGG CTC TGC AAA AAG AA - 3’; APP knockout reverse: 5’ - GCC AGA GGC CAC TTG TGT AG - 3’; common: 5’ - AAA ACC AAA CCA GGA AAT GC −3’. All procedures were approved by the Institutional Animal Care and Use Committee and were in compliance with NIH guidelines.