Eye specific transcription start site (TSS) of mouse Itpr1. Mus musculus strain:C57Bl/6J

Mutations in ITPR1 cause ataxia and aniridia in individuals with Gillespie syndrome (GLSP). However, the underlying pathogenic mechanism of aniridia remains unclear. We identified a de novo GLSP mutation hotspot in the 3-region of ITPR1 in five individuals with GLSP. Mutations or deletions in the anterior half of ITPR1 result in autosomal-dominant neurological disorders, spinocerebellar ataxia; however, individuals with spinocerebellar do not exhibit aniridia. Therefore, we hypothesized the existence of an undiscovered TSS near the 3-end of ITPR. To confirm this hypothesis, we performed RNA-seq using total RNA extracted from the eyes and brains of generated genetically modified mice harboring a V5-tag in frame at the 3-terminus of Itpr1. RNA-seq and immunoblotting revealed an eye-specific transcript encoding 218 amino acids of Itpr1.