Huntingtin-associated protein 1 (HAP1) was identified as an interactor of the gene product (Huntingtin) responsible for Huntington's disease and found to be a core component of the stigmoid body. Even though HAP1 is highly expressed in the brain, detailed information on HAP1 distribution has not been fully described. Focusing on the neuroanatomical analysis of HAP1-mRNA expression using in situ hybridization histochemistry, the present study clarified its detailed regional distribution in the entire mouse brain. Mouse HAP1 (Hap1)-mRNAs were abundantly expressed in the limbic-related forebrain regions and midline/periventricular brainstem regions including the olfactory bulb, limbic-associated cortices, hippocampus, septum, amygdala, bed nucleus of the stria terminalis, preoptico-hypothalamic regions, central gray, raphe nuclei, locus coeruleus, parabrachial nuclei, nucleus of the solitary tract, and area postrema. In contrast, little expression was detected in the striatum and thalamus, implying that Hap1 is associated with neurodegeneration-sparing regions rather than target lesions in Huntington's disease. The distribution pattern, resembling that of the stigmoid body, suggests that HAP1 and the stigmoid body are implicated in protection from neuronal death rather than induction of neurodegeneration in Huntington's disease, and that they play an important role in integrating instinct behaviors and underlying autonomic, visceral, arousal, drive, memory, and neuroendocrinergic functions, particularly during extensive homeostatic or emotional processes. These data will provide an important morphological base for a future understanding of functions of HAP1 and the stigmoid body in the brain.
