Animal Models of Kennedy Disease

Since the identification of the polyglutamine repeat expansion responsible for Kennedy disease (KD) more than a decade ago, several laboratories have created animal models for KD. The slowly progressive nature of KD, its X-linked dominant mode of inheritance, and its recently elucidated hormone dependence have made the modeling of this lower motor neuron disease uniquely challenging. Several models have been generated in which variations in specificity, age of onset, and rate of progression have been achieved. Animal models that precisely reproduce the motor neuron specificity, delayed onset, and slow progression of disease may not support preclinical therapeutics testing, whereas models with rapidly progressing symptoms may preclude the ability to fully elucidate pathogenic pathways. Drosophila models of KD provide unique opportunities to use the power of genetics to identify pathogenic pathways at work in KD. This paper reviews the new wealth of transgenic mouse and Drosophila models for KD. Whereas differences, primarily in neuropathological findings, exist in these models, these differences may be exploited to begin to elucidate the most relevant pathological features of KD.