Distinct point mutations in the RET proto-oncogene are the cause of the 
inherited multiple endocrine neoplasia type 2 syndromes (MEN 2), and the 
congenital gut disorder Hirschsprung disease. The site and type of these 
mutations suggests that they have differing effects on the activity of the 
receptor tyrosine kinase encoded by RET. The normal function of the RET receptor 
tyrosine kinase has yet to be determined. However, this has been investigated by 
the inactivation of the RET gene in transgenic mice. The developmental 
abnormalities apparent in these mice, together with the observation that the 
major tissues affected in MEN 2 and Hirschsprung disease have a common origin in 
the embryonal neural crest, suggest that RET encodes a receptor for a 
developmental regulator involved in the genesis of a variety of neural crest 
derivatives, and in the organogenesis of the kidney.