Of these, MSH3 has become a major focus for therapeutic development because loss of MSH3 appears to be well tolerated.36 In preparation for the preclinical evaluation of these potential treatments, we genetically ablated Msh3 in the zQ175 knock-in mouse model of Huntington's disease to determine the maximum benefit of targeting Msh3 in this model. This evidence concerns the gene MSH3 and juvenile Huntington disease.