title: Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1.
abstract: 22q11-deletion (DiGeorge/velocardiofacial) syndrome (22q11DS) is modeled by mutation of murine transcription factor Tbx1. As part of efforts to identify transcriptional targets of Tbx1, we analyzed the transcriptome of the pharyngeal region of Df1/+;Tbx1+/- embryos at 9.5 days of embryonic development using two independent microarray platforms. In this model, embryos are null for Tbx1, with hemizygosity of genes in cis with Tbx1 on one chromosome providing a positive control for array sensitivity. Reduced mRNA levels of genes deleted from Df1 were detected on both platforms. Expression level filtering and statistical analysis identified several genes that were consistently differentially expressed between mutant and wild type embryos. Real-time quantitative PCR and in situ hybridization validated diminished expression of Pax9 and Gcm2, genes known to be required for normal thymus and parathyroid gland morphogenesis, whereas Pax1, Hoxa3, Eya1, and Foxn1, which are similarly required, were not down-regulated. Gbx2, a gene required for normal arch artery development, was down-regulated specifically in the pharyngeal endoderm and the posterior part of pharyngeal arch 1, and is a potential point of cross talk between the Tbx1 and Fgf8 controlled pathways. These experiments highlight which genes and pathways potentially affected by lack of Tbx1, and whose role may be explored further by testing for epistasis using mouse mutants.
authors.affiliation: Molecular Medicine Unit, Institute of Child Health, London WC1N 1EH, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ivins
authors.forename: Kelly
authors.initials: K
authors.lastname: Lammerts van Beuren
authors.forename: Catherine
authors.initials: C
authors.lastname: Roberts
authors.forename: Chela
authors.initials: C
authors.lastname: James
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lindsay
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldini
authors.forename: Paris
authors.initials: P
authors.lastname: Ataliotis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scambler
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D051379:Mice / Q000196:embryology* / Q000235:genetics*; D008817:Mice, Mutant Strains; D046228:Microarray Analysis; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D016133:Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; C488759:Pax9 protein, mouse; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse