IMPAIRED DEVELOPMENT OF THE THYROID AND THYMUS IN ENDOTHELIN-1 KNOCKOUT MICE

We have previously demonstrated that endothelin-1 (ET-1) is essential to the development of neural crest-derived craniofacial and cardiovascular structures. In this study we evaluated the intrauterine growth and development of the thyroid and thymus glands in Edn1-/- homozygous mice. Edn1-/- homozygous mice were smaller than their heterozygous or wild-type littermates (about 90% of normal body weight). The thyroid and thymus of Edn1-/- homozygous mice were smaller than those of normal mice and were not fused in the midline, resulting in two separate lobules. The thymus of Edn1-/- homozygous mice is not descended into the normal position. These results suggest that ET-1 is important for normal development of the glands in the neck region, as well as for systemic growth. The combination of abnormalities in Edn1-/- homozygous mice suggests that these mice might serve as an animal model for the human diseases DiGeorge syndrome and velocardiofacial syndrome.