A missense mutation in zbtb17 blocks the earliest steps of T cell differentiation in zebrafish

Abstract

T cells are an evolutionarily conserved feature of the adaptive immune systems of vertebrates. Comparative studies using evolutionarily distant species hold great promise for unraveling the genetic landscape underlying this process. To this end, we used ENU mutagenesis to generate mutant zebrafish with specific aberrations in early T cell development. Here, we describe the identification of a recessive missense mutation in the transcriptional regulator zbtb17 (Q562K), which affects the ninth zinc finger module of the protein. Homozygous mutant fish exhibit an early block of intrathymic T cell development, as a result of impaired thymus colonization owing to reduced expression of the gene encoding the homing receptor ccr9a, and inefficient T cell differentiation owing to reduced expression of socs1a. Our results reveal the zbtb17-socs1 axis as an evolutionarily conserved central regulatory module of early T cell development of vertebrates.