other polyglutamine expansion diseases, however rodent model studies have shown significantly later formation of nuclear inclusions of mutant proteins in cerebellum and spinal cord neurons than in cortical and hippocampal neurons, which typically show only mild degeneration in SCA1 persons, suggesting a more complicated mechanism. Ataxin-null mice are shown to exhibit reduced motor and spatial learning, suggesting ataxin 1 plays a role in synaptic plasticity and interactions between the motor neurons and the hippocampus. However mice lacking both copies of ataxin 1 do not develop progressive neurological symptoms or show signs of atrophy, suggesting that toxicity of the mutated protein, not loss of function, is the main mechanism for SCA1 pathology. A comparison of mRNA between ataxin null mice and mice with ataxin1154Q/+ shows that there are common changes in gene expression, including upregulation of genes known to be repressed by an ataxin 1/CIC complex. This suggest that, while not the primary mechanism, a loss of ataxin 1 function contributes to the pathogenesis of SCA1. While the ataxin 1/CIC complex losses some of its regulatory function with expanded ataxin 1, CIC knockout mice do not show degeneration, suggesting interactions between ataxin 1 and CIC mediate most of the toxic effects. Mutant ataxin-1 also known to alter the neural circuitry of the developing cerebellum, which may lead to later vulnerability of Purkinje cells and suggests the existence of non-cell autonomous toxicity. The various interactions of ataxin 1 lead to many possible factors that can exasperate or moderate toxicity of its mutant form. Wild type ataxin 1 is quickly degraded in the cytoplasm, but can be stabilized by phosphorylation and 14-3-3 binding as needed by the cell. SCA1 positive mice haplodeficient in 14-3-3ε+/- were shown not to exhibit cerebellar degeneration but still exhibited lethal bulbar degeneration, suggesting that cerebellar atrophy may be related to increased stability of the expanded ataxin 1 protein and that there may be different pathogenic mechanisms for different regions of the brain. The site of phosphorylation is the serine at the 776th residue in ataxin 1. Similar to those that lack 14-3-3 proteins, mice with this residue replaced with alanine do not exhibit cerebellar syndrome. Similarly, removal of the AXH domain from ataxin 1 prevents aberrant interactions with growth factor independent transcription repressor 1 that leads to GFI1 degradation in the proteasome. The expanded polyglutamine region results in increased affinity of the ataxin 1 AXH domain for certain