There and back again: Autoimmune Polyendocrinopathy Syndrome Type I and the Aire knockout mouse

Autoimmune Polyendocrinopathy Syndrome Type I (APS1) is a severe human multiorgan autoimmune disorder, caused by mutations in the gene AIRE. Following this determination, a mouse model for the disease was rationally designed by knocking out the murine homologue, Aire. The Aire knockout mouse has demonstrated that Aire initiates immune tolerance via promiscuous transcription of organ-specific genes in the thymus. Recent studies using the Aire knockout mouse have demonstrated gene-dose dependency and disease modifier loci, returning the onus of exploration to human genetics.

Section editor:Daniel Altmann – Human Disease Immunogenetics Group, Hammersmith Hospital, London, UK