Iwanami, N., Mateos, F., Hess, I., Riffel, N., Soza-Ried, C., Schorpp, M., and Boehm, T. (2011) Genetic Evidence for an Evolutionarily Conserved Role of IL-7 Signaling in T Cell Development of Zebrafish. Journal of immunology (Baltimore, Md. : 1950). 186(12):7060-6.
In mammals, the cytokine IL-7 is a key regulator of various aspects of lymphocyte differentiation and homeostasis. Because
of the difficulty of identifying cytokine homologs in lower vertebrates and the paucity of assay systems and reagents, the
degree of functional conservation of cytokine signaling pathways, particularly those pertaining to lymphocyte development,
is unclear. In this article, we report on the analysis and characterization of three zebrafish mutants with severely impaired
thymopoiesis. The identification of affected genes by positional cloning revealed components of the IL-7 signaling pathway.
A presumptive null allele of the zebrafish homolog of the IL-7Rα–chain causes substantially reduced cellularity of the thymus
but spares B cell development in the kidney. Likewise, nonsense mutations in the zebrafish homologs of janus kinases JAK1
and JAK3 preferentially affect T cell development. The functional interactions of the cytokine receptor components were examined
in the three groups of fish hetero- or homozygous for either il7r and jak1, il7r and jak3, or jak1 and jak3 mutations. The differential effects on T cell development arising from the different genotypes could be explained on the
basis of the known structure of the mammalian IL-7R complex. Because IL-7 signaling appears to be a universal requirement
for T cell development in vertebrates, the mutants described in this article represent alternative animal models of human
immunodeficiency syndromes amenable to large-scale genetic and chemical screens.