A wide spectrum of birth defects is caused by deletions of the DiGeorge syndrome chromosomal region at 22q11. Characteristic features include cranio-facial, cardiac and thymic malformations, which are thought to arise form 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 22q11, but nothing is known about the expression of these genes in mammalian embryos. We report here the isolation of several murine embryonic cDNAs of the DiGeorge syndrome candidate gene HIRA. We identified several alternatively spliced transcripts. Sequence analysis reveals that Hira bears homology to the p60 subunit of the human Chromatin Assembly 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 development show that Hira is ubiquitously expressed. However, higher levels of transcripts are detected in the cranial neural folds, frontonasal mass, 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 haploinsufficiency of HIRA contributes to at least some of the features of the DiGeorge phenotype.

*Cell Cycle Proteins, *Chromosomal Proteins, Non-Histone, *Chromosomes, Human, Pair 22, Alternative Splicing, Amino Acid Sequence, Animals, Base Sequence, Branchial Region/metabolism, Chromosome Aberrations/*genetics, Chromosome Disorders, Cloning, Molecular, DNA, Complementary, DNA-Binding Proteins/genetics, DiGeorge Syndrome/*genetics, Embryo/metabolism, Exons, Female, Gastrula, Gene Expression, Humans, Limb Bud/metabolism, Male, Mice, Molecular Sequence Data, Neural Crest/metabolism, Nuclear Proteins/*genetics, Sequence Homology, Amino Acid, Transcription Factors/*genetics
hdl.handle.net/1765/8655
Human Molecular Genetics
Erasmus MC: University Medical Center Rotterdam

Wilming, L.G, Snoeren, C.A, Rijswijk, A.L, Meijers, C, & Grosveld, F.G. (1997). The murine homologue of HIRA, a DiGeorge syndrome candidate gene, is expressed in embryonic structures affected in human CATCH22 patients. Human Molecular Genetics. Retrieved from http://hdl.handle.net/1765/8655