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.
A cerebellar exam may include saying phrases with many consonants to detect scanning speech, detecting horizontal gaze nystagmus by following a finger with the eyes, performing rapid alternating movements like rotating a hand from palm to back repeatedly, testing the Holmes rebound phenomenon, and testing patellar reflex for hypotonia or hypertonia. Common scales include the International Cooperative Ataxia Rating Scale (ICARS) and Scale for the Assessment and Rating of Ataxic Disorders (SARA) for evaluating the severity of ataxia as a symptom. ICARS measures on a 100 scale, where 0 is normal function and 100 is the highest possible impairment, assigning different point values for different tests. The tests are divided into categories evaluating posture and gait, kinetic functions, speech, and oculomotor functions. While these categories create useful categorization to assess which areas need to be focused on in therapies, this redundancy results in a longer test time, which can skew results of tests performed at the end of a session; and can result in contradictory scores. SARA is a shorter exam, evaluated on a scale of 0 to 40, where again zero is normal function and 40 is highest possible impairment. It comprises eight tests: gait, stance, finger chase, finger-to-nose test, fast alternating hand movements, heel-shin slide, and three limb kinectic function tests. Differential diagnosis
Differential diagnosis of SCAs by clinical methods is difficult because these diseases are clinically heterogenous and there is significant variance between the expression of individual cases.