Regulation of 22q11 orthologous genes during mouse development

22q11-deletion syndrome (22q11DS) is a developmental anomaly caused by a microdeletion on human chromosome 22q11. Although mouse models indicated Tbx1 as the gene responsible of the syndrome, the phenotypic spectrum of del22q11 patients is complex suggesting that gene-gene and gene-environment interactions, probably during embryonic development, are crucial in delineating the pathogenesis of 22q11DS. In order to define cis-acting regulatory effects of 22q11Ds haploinsufficiency during development we analysed the expression pattern of MM16 mouse genes, that is the syntenic region to 22q11, in RNA from total embryos at different stages (from 4.5 dpc to 14.5 dpc; corresponding to pharyngeal development) by a low density microarray (22q11DS-chip). Keywords: time-course Deletion of 22q11.2 chromosomal region causes the most common microdeletion syndrome in man with an incidence of approximately 1:4000 live births (Scambler, 2000). The major malformations include congenital heart defects such as truncus arteriosus (TA) and interrupted aortic arch type B (IAA-B), hypo/aplasia of the parathyroid glands, hypo/aplasia of the thymus gland, and craniofacial dysmorphism. However more than 180 clinical symptoms are due to 22q11 microdeletion (Ryan et al, 1997); in particular the psychiatric disorders are one of the more prevalent phenotype in adult patients (Basset et al., 2003). An unsolved question regarding 22q11 deletions is whether the associated congenital defects are caused by a single dose-dependent 22q11 gene or rather by the combined loss of multiple linked genes that may act in a common pathway or in parallel during a critical period of pharyngeal development. In order to answer to this question we have turned out our attention at analysing the expression level of 68 murine genes, 39 hortologues to human 22q11 genes and 29 mapping outside. The expression level of these 68 genes was analysed in mouse embryos at different stages (from 4.5 dpc to 14.5 dpc), corresponding to the pharyngeal development. The RNA reference used in this study was obtained by pooling different CD1 mouse embryos at 18.5 dpc; total RNA was isolated by the TRIZOL standard protocol (Invitrogen).