Because mutations affecting the regions of the LHX3 protein involved in these interactions are associated with severe pediatric human diseases, these observations may have relevance to our understanding of the aberrant mechanisms underlying such diseases and may provide insights into the etiology of human endocrine diseases and allow future therapies and genetic counseling. Huntington disease is a devastating, incurable neurodegenerative condition, caused by CAG repeat expansion in the IT15 gene, which encodes an expanded polyglutamine tract in the target protein, huntingtin. One barrier to rapid development of therapies is the difficulty and expense in carrying out preclinical in vivo trials of PK 44 phosphate candidate therapeutic compounds. This is due to multiple factors, especially inter-animal variability that requires large numbers of animals over relatively long study periods, and the challenge of drug delivery to the CNS. The R6/2 mouse is widely used to study HD pathogenesis and test therapeutic leads. It expresses the first exon of the expanded Htt gene, which produces a highly neurotoxic and aggregation-prone protein. It exhibits rapid and uniform symptom onset at about 5�C6 weeks of age, with death at about 14�C19 weeks. The R6/2 mouse has been reported previously to develop retinopathy, but the histopathological descriptions have been only of the later-stage retinal phenotype at about 10 weeks of age, and no functional studies have been reported in this line. By contrast, the R6/1 line, which also expresses Htt exon 1, has later onset, and much later death. Its retinal pathology has been more thoroughly PF 750 studied. The retinal phenotype appears to be virtually identical in character in the two lines, differing only in time of onset and rate of degeneration. In the R6/1 line, measurement of retinal function by electroretinography reveals decrements that precede histological changes, suggesting that Htt toxicity manifests first with neural dysfunction. Since the rapid symptom evolution in R6/2 mice is much more favorable for assessing therapeutic intervention, we have carefully characterized the pathologic and physiologic features of retinal degeneration in this model.