title: Co-expression of FBN1 with mesenchyme-specific genes in mouse cell lines: implications for phenotypic variability in Marfan syndrome.
abstract: Mutations in the human FBN1 gene cause Marfan syndrome, a complex disease affecting connective tissues but with a highly variable phenotype. To identify genes that might participate in epistatic interactions with FBN1, and could therefore explain the observed phenotypic variability, we have looked for genes that are co-expressed with Fbn1 in the mouse. Microarray expression data derived from a range of primary mouse cells and cell lines were analysed using the network analysis tool BioLayout Express(3D). A cluster of 205 genes, including Fbn1, were selectively expressed by mouse cell lines of different mesenchymal lineages and by mouse primary mesenchymal cells (preadipocytes, myoblasts, fibroblasts, osteoblasts). Promoter analysis of this gene set identified several candidate transcriptional regulators. Genes within this co-expressed cluster are candidate genetic modifiers for Marfan syndrome and for other connective tissue diseases.
authors.affiliation: The Roslin Institute, University of Edinburgh, Midlothian, UK. kim.summers@roslin.ed.ac.uk
authors.forename: Kim M
authors.initials: KM
authors.lastname: Summers
authors.forename: Sobia
authors.initials: S
authors.lastname: Raza
authors.forename: Erik
authors.initials: E
authors.lastname: van Nimwegen
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Freeman
authors.forename: David A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016000:Cluster Analysis; D000071838:Fibrillin-1; D000071837:Fibrillins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics / Q000473:pathology; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D014157:Transcription Factors; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse