Several human syndromes, including DiGeorge (DGS) and related syndromes are associated with microdeletions and hemizygosity of human chromosome 22q11. The majority of these cases arise from large deletions (approximately 2 Mb), the extent of which does not appear to correlate with the observed phenotype and therefore the exact genetic nature of these disorders remains unclear. In order to study this further, we plan to recreate these microdeletions in the mouse using the LoxP and Cre recombinase system. A comparison of different deletions and their transgenic complementation should allow the phenotypic contribution of subregions and genes within the DGS critical region to be elucidated. Towards this aim, we have identified mouse homologues within the DGS critical region, and determined their genomic organization and the conservation of synteny. The first steps towards creating microdeletions have been completed, with LoxP sites targeted to two locations flanking the critical region. In addition, the phenotypic contribution of a single gene within the critical region, (Idd), is being analyzed through a single gene knockout.
