title: Dynamic changes in gene expression profiles of 22q11 and related orthologous genes during mouse development.
abstract: 22q11 deletion syndrome (22q11DS) is a developmental anomaly caused by a microdeletion on human chromosome 22q11. Although mouse models indicate that Tbx1 is the gene responsible for the syndrome, the phenotypic spectrum of del22q11 patients is complex suggesting that gene-gene and gene-environment interactions are operative in delineating the pathogenesis of 22q11DS. In order to study the regulatory effects of 22q11 haploinsufficiency during development, the expression pattern of the orthologous MM16 genes was analysed in total embryos at different stages (from 4.5 dpc to 14.5 dpc; corresponding to pharyngeal development) by using a low-density oligonucleotide microarray (the "22q11DS-chip"). This microarray consists of 39 mouse genes orthologous to the 22q11 human ones and 29 mouse target genes selected on the basis of their potential involvement in biological pathways regarding 22q11 gene products. Expression level filtering and statistical analysis identified a set of genes that was consistently differentially expressed (FC>+/-2) during specific developmental stages. These genes show a similar profile in expression (overexpression or underexpression). Quantitative real-time PCR analyses showed an identical expression pattern to that found by microarrays. A bioinformatic screening of regulative sequence elements in the promoter region of these genes, revealed the existence of conserved transcription factor binding sites (TFBSs) in co-regulated genes which are functionally active at 4.5, 8.5 and 14.5 dpc. These data are likely to be helpful in studying developmental anomalies detected in del22q11 patients.
authors.affiliation: Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Rome, Italy. amati@med.uniroma2.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Amati
authors.forename: Michela
authors.initials: M
authors.lastname: Biancolella
authors.forename: Alessio
authors.initials: A
authors.lastname: Farcomeni
authors.forename: Stefania
authors.initials: S
authors.lastname: Giallonardi
authors.forename: Susana
authors.initials: S
authors.lastname: Bueno
authors.forename: Daniela
authors.initials: D
authors.lastname: Minella
authors.forename: Lucia
authors.initials: L
authors.lastname: Vecchione
authors.forename: Giovanni
authors.initials: G
authors.lastname: Chillemi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
mesh_terms: D000818:Animals; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010614:Pharynx / Q000196:embryology / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D026801:Synteny; D013997:Time Factors