Striosome-matrix pathology and motor deficits in the YAC128 mouse model of Huntington's disease

Huntington's disease is characterized by striatal degeneration and progressive motor deficits. To examine striatal compartment-specific pathology and its relation to motor symptoms, we used immunohistochemistry to identify and measure the striosomes and matrix of 7-13-month-old YAC128 and wild type (WT) mice that were previously tested on motor tasks. Compared to WTs, 13-month-old YAC128s showed volume shrinkage in striosomes, and cell loss in both compartments. The percent cell loss was greater in striosomes than matrix. Striosome volume and cell loss was greatest in the dorsolateral striatum. YAC128 rotarod and balance beam deficits preceded volume and cell loss. At 13 months, YAC128 balance beam slips and striosome cell number were inversely correlated. The results show that pathology in older YAC128s manifests as an abnormal striosome to matrix ratio and suggest that this imbalance can contribute to some motor symptoms.