title: Global analysis of gene expression in the developing brain of Gtf2ird1 knockout mice.
abstract: BACKGROUND
  Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by a hemizygous deletion of a 1.5 Mb region on chromosome 7q11.23 encompassing 26 genes. One of these genes, GTF2IRD1, codes for a putative transcription factor that is expressed throughout the brain during development. Genotype-phenotype studies in patients with atypical deletions of 7q11.23 implicate this gene in the neurological features of WBS, and Gtf2ird1 knockout mice show reduced innate fear and increased sociability, consistent with features of WBS. Multiple studies have identified in vitro target genes of GTF2IRD1, but we sought to identify in vivo targets in the mouse brain.
  
  
  RESULTS
  We performed the first in vivo microarray screen for transcriptional targets of Gtf2ird1 in brain tissue from Gtf2ird1 knockout and wildtype mice at embryonic day 15.5 and at birth. Changes in gene expression in the mutant mice were moderate (0.5 to 2.5 fold) and of candidate genes with altered expression verified using real-time PCR, most were located on chromosome 5, within 10 Mb of Gtf2ird1. siRNA knock-down of Gtf2ird1 in two mouse neuronal cell lines failed to identify changes in expression of any of the genes identified from the microarray and subsequent analysis showed that differences in expression of genes on chromosome 5 were the result of retention of that chromosome region from the targeted embryonic stem cell line, and so were dependent upon strain rather than Gtf2ird1 genotype. In addition, specific analysis of genes previously identified as direct in vitro targets of GTF2IRD1 failed to show altered expression.
  
  
  CONCLUSIONS
  We have been unable to identify any in vivo neuronal targets of GTF2IRD1 through genome-wide expression analysis, despite widespread and robust expression of this protein in the developing rodent brain.
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors: Jennifer
authors: J
authors: O'Leary
authors: Lucy R
authors: LR
authors: Osborne
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D056726:Genetic Association Studies; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C486558:Gtf2ird1 protein, mouse; D009124:Muscle Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; D015534:Trans-Activators