INDUCTION OF A NEW METALLOTHIONEIN ISOFORM (MT-IV) OCCURS DURING DIFFERENTIATION OF STRATIFIED SQUAMOUS EPITHELIA

A new member of the metallothionein (MT) gene family was discovered th at lies about 20 kb 5' of the MT-III gene in both mouse and human. The MT-IV proteins are highly conserved in both species and have a glutam ate insertion at position 5 relative to the classical MT-I and MT-II p roteins. Murine MT-IV mRNA appears to be expressed exclusively in stra tified squamous epithelia associated with oral epithelia, esophagus, u pper stomach, tail, footpads, and neonatal skin. The MT derived from t ongue epithelium contains both zinc and copper. Many of these epitheli a develop parakaratosis during zinc deficiency in the rat. In situ hyb ridization reveals intense labeling of MT-IV mRNA in the differentiati ng spinous layer of cornified epithelia, whereas MT-I is expressed pre dominantly in the basal, proliferative layer; thus, there is a switch in MT isoform synthesis during differentiation of these epithelia. We suggest that MT-IV plays a special role in regulating zinc metabolism during the differentiation of stratified epithelia.