THE MURINE HOMOLOG OF HIRA, A DIGEORGE-SYNDROME CANDIDATE GENE, IS EXPRESSED IN EMBRYONIC STRUCTURES AFFECTED IN HUMAN CATCH22 PATIENTS

A wide spectrum of birth defects is caused by deletions of the DiGeorg e syndrome chromosomal region at 22q11, Characteristic features includ e cranio-facial, cardiac and thymic malformations, which are thought t o arise from disturbances in the interactions between hindbrain neural crest cells and the endoderm of the pharyngeal pouches, Several genes have been identified in the shortest region of deletion overlap at 22 q11, but nothing is known about the expression of these genes in mamma lian embryos, We report here the isolation of several murine embryonic cDNAs of the DiGeorge syndrome candidate gene HIRA. We identified sev eral alternatively spliced transcripts. Sequence analysis reveals that Hira bears homology to the p60 subunit of the human Chromatin Assembl y Factor I and yeast Hir1p and Hir2p, suggesting that Hira might have some role in chromatin assembly and/or histone regulation. Whole mount in situ hybridization of mouse embryos at various stages of developme nt show that Hira is ubiquitously expressed, However, higher levels of transcripts are detected in the cranial neural folds, frontonasal mas s, first two pharyngeal arches, circumpharyngeal neural crest and the limb buds, Since many of the structures affected in DiGeorge syndrome derive from these Hira expressing cell populations we propose that hap loinsufficiency of HIRA contributes to at least some of the features o f the DiGeorge phenotype.