Combined Pituitary Hormone Deficiency in -Knockout Zebrafish.

LIM homeobox 4 (LHX4) is a transcription factor crucial for anterior pituitary (AP) development. Patients with mutation suffer from combined pituitary hormone deficiency (CPHD), short statures, reproductive and metabolic disorders and lethality in some cases. -knockout (KO) mice fail to develop a normal AP and die shortly after birth. Here, we characterize a zebrafish -KO model to further investigate the importance of in pituitary gland development and regulation. At the embryonic and larval stages, these fish express lower levels of mRNA compared with their wildtype siblings. In adult -KO fish, the expressions of pituitary hormone-encoding transcripts, including (, (, ( and (, are reduced, the promoter-driven expression in corticotrophs is dampened and -producing gonadotrophs are severely depleted. In contrast to -KO mice, Lhx4-deficient fish survive to adulthood, but with a reduced body size. Importantly, -KO males reach sexual maturity and are reproductively competent, whereas the females remain infertile with undeveloped ovaries. These phenotypes, which are reminiscent of those observed in CPHD patients, along with the advantages of the zebrafish for developmental genetics research, make this -KO fish an ideal vertebrate model to study the outcomes of mutation.