Targeting MSH3 has significant therapeutic potential for Huntington's disease and other trinucleotide repeat disorders,34 and a wide range of MSH3-targeting modalities are under development.29,66 Our data indicate that whilst ablation of MSH3 prevented somatic CAG repeat expansion in zQ175 mice, this model will not be useful for evaluating these MSH3-targeting treatments, and that knock-in mice with shorter CAG repeat mutations should be used. The gene discussed is MSH3; the disease is juvenile Huntington disease.