Isolation and embryonic expression of the novel mouse gene Hic1, the homologue of HIC1, a candidate gene for the Miller-Dieker syndrome

The human gene HIC1 (hypermethylated in cancer) maps to chromosome 17p13.3 and is deleted in the contiguous gene disorder Miller-Dieker syndrome (MDS) [Makos-Wales et al. (1995) Nature Med., 1, 570-577; Chong et al, (1996) Ge nome Res., 6, 735-741]. We isolated the murine homologue Hid, encoding a zi nc-finger protein with a poxvirus and zinc-finger (POZ) domain and mapped i t to mouse chromosome 11 in a region exhibiting conserved synteny to human chromosome 17, Comparison of genomic and cDNA sequences predicts two exons for the murine Hid. The second exon exhibits 88% identity to the human HIC1 on DNA level. During embryonic development, Hid is expressed in mesenchyme s of the sclerotomes, lateral body wall, limb and cranio-facial regions emb edding the outgrowing peripheral nerves during their differentiation, Durin g fetal development, Hid additionally is expressed in mesenchymes apposed t o precartilaginous condensations, at many interfaces to budding epithelia o f inner organs, and weakly in muscles. We observed activation of Hid expres sion in the embryonic anlagen of many tissues displaying anomalies in MDS p atients. Besides lissencephaly, MDS patients exhibit facial dysmorphism and frequently additional birth defects, e.g. anomalies of the heart, kidney, gastrointestinal tract and the limbs (OMIM 247200), Thus, HIC1 activity may correlate with the defective development of the nose, jaws, extremities, g astrointestinal tract and kidney in MDS patients.