Developing Models of Aristaless-related homeobox mutations

Mutations in the Aristaless-related homeobox gene () have been causally linked to a variety of neurological conditions, particularly, infantile spasms syndrome. is a developmentally regulated homeobox transcription factor with expression both in the ganglionic eminence and the cortical ventricular zone early in development. Postnatally, the expression pattern is restricted to GABAergic neurons in the cortex and basal ganglia. During development, functions primarily as a transcriptional repressor: modulating migration and fate specification of interneurons and controlling ventricular zone proliferation. How loss of function of leads to an epilepsy phenotype is poorly understood. Three genetically modified mice lines have been generated to address this issue. These models each develop epilepsy and all have changes in interneuron subtype patterns strongly implicating alterations of interneuron development as a cause of epilepsy. Analysis of these models will both further the molecular understanding of the function of and allow dissection of the pathophysiological properties of the related epilepsies. This chapter will review the current knowledge of the function of , the mouse models, and discuss how these models can lead to a better understanding of the role of interneuron loss in the development of epilepsy during early childhood.