Microarray analysis of the Df1 mouse model of the 22q11 deletion syndrome |
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Authors: | Katrina Prescott Sarah Ivins Mike Hubank Elizabeth Lindsay Antonio Baldini Peter Scambler |
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Institution: | (1) Molecular Medicine Unit, Institute of Child Health, 30 Guilford St., London, WC1N 1EH, UK;(2) Molecular Haematology and Cancer Biology Unit, Institute of Child Health, 30 Guilford St., London, WC1N 1EH, UK;(3) Department of Pediatrics (Cardiology), Baylor College of Medicine, 6621 Fannin St., FC430.09, Houston, Texas 77030, USA |
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Abstract: | The 22q11 deletion syndrome (22q11DS; DiGeorge/velo-cardio-facial syndrome) primarily affects the structures comprising the pharyngeal arches and pouches resulting in arch artery, cardiac, parathyroid, thymus, palatal and craniofacial defects. Tbx1 haploinsufficiency is thought to account for the main structural anomalies observed in the 22q11DS. The Df1 deleted mouse provides a model for 22q11DS, the deletion reflecting Tbx1 haploinsufficiency in the context of the deletion of 21 adjacent genes. We examined the expression of genes in Df1 embryos at embryonic day (E) 10.5, a stage when the arch-artery phenotype is fully penetrant. Our aims were threefold, with our primary aim to identify differentially regulated genes. Second, we asked whether any of the genes hemizygous in Df1 were dosage compensated to wild type levels, and third we investigated whether genes immediately adjacent to the deletion were dysregulated secondary to a position effect. Utilisation of oligonulceotide arrays allowed us to achieve our aims with 9 out of 12 Df1 deleted genes passing the stringent statistical filtering applied. Several genes involved in vasculogenesis and cardiogenesis were validated by real time quantitative PCR (RTQPCR), including Connexin 45, a gene required for normal vascular development, and Dnajb9 a gene implicated in microvascular differentiation. There was no evidence of any dosage compensation of deleted genes, suggesting this phenomenon is rare, and no dysregulation of genes mapping immediately adjacent to the deletion was detected. However Crkl, another gene implicated in the 22q11DS phenotype, was found to be downregulated by microarray and RTQPCR. |
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Keywords: | DiGeorge syndrome 22q11DS Tbx1 Microarray Haploinsufficiency Gene dosage |
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