title: SLUG (SNAI2) overexpression in embryonic development.
abstract: The Snail-related zinc-finger transcription factor, SLUG (SNAI2), is critical for the normal development of neural crest-derived cells and loss-of-function SLUG mutations have been proven to cause piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. However, little is known about the consequences of SLUG overexpression in embryonic development. We report SLUG duplication in a child with a unique de novo 8q11.2-->q13.3 duplication associated with tetralogy of Fallot, submucous cleft palate, renal anomalies, hypotonia and developmental delay. To investigate the effects of Slug overexpression on development, we analyzed mice carrying a Slug transgene. These mice were morphologically normal at birth, inferring that Slug overexpression is not sufficient to cause overt morphogenetic defects. In the adult mice, there was a 20% incidence of sudden death, cardiomegaly and cardiac failure associated with incipient mesenchymal tumorigenesis. These findings, while not directly implicating Slug in congenital and acquired heart disease, raise the possibility that Slug overexpression may contribute to specific cardiac phenotypes and cancer development.
authors.affiliation: Laboratorio 13, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Salamanca, Spain.
authors.forename: P A
authors.initials: PA
authors.lastname: Pérez-Mancera
authors.forename: I
authors.initials: I
authors.lastname: González-Herrero
authors.forename: K
authors.initials: K
authors.lastname: Maclean
authors.forename: A M
authors.initials: AM
authors.lastname: Turner
authors.forename: M-Y
authors.initials: MY
authors.lastname: Yip
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-Martín
authors.forename: J L
authors.initials: JL
authors.lastname: García
authors.forename: C
authors.initials: C
authors.lastname: Robledo
authors.forename: T
authors.initials: T
authors.lastname: Flores
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez-Adán
authors.forename: B
authors.initials: B
authors.lastname: Pintado
authors.forename: I
authors.initials: I
authors.lastname: Sánchez-García
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D047108:Embryonic Development / Q000235:genetics*; D020440:Gene Duplication; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D051379:Mice; D008822:Mice, Transgenic; D009693:Nucleic Acid Hybridization; D000071250:Snail Family Transcription Factors; D013771:Tetralogy of Fallot / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014314:Trisomy
chemical_list: C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors