title: Expression of the CTCFL Gene during Mouse Embryogenesis Causes Growth Retardation, Postnatal Lethality, and Dysregulation of the Transforming Growth Factor β Pathway.
abstract: CTCFL, a paralog of CTCF, also known as BORIS (brother of regulator of imprinted sites), is a testis-expressed gene whose function is largely unknown. Its product is a cancer testis antigen (CTA), and it is often expressed in tumor cells and also seen in two benign human vascular malformations, juvenile angiofibromas and infantile hemangiomas. To understand the function of Ctcfl, we created tetracycline-inducible Ctcfl transgenic mice. We show that Ctcfl expression during embryogenesis results in growth retardation, eye malformations, multiorgan pathologies, vascular defects, and neonatal death. This phenotype resembles prior mouse models that perturb the transforming growth factor β (TGFB) pathway. Embryonic stem (ES) cells with the Ctcfl transgene reproduce the phenotype in ES cell-tetraploid chimeras. Transcriptome sequencing of the Ctcfl ES cells revealed 14 genes deregulated by Ctcfl expression. Bioinformatic analysis revealed the TGFB pathway as most affected by embryonic Ctcfl expression. Understanding the consequence of Ctcfl expression in nontesticular cells and elucidating downstream targets of Ctcfl could explain the role of its product as a CTA and its involvement in two, if not more, human vascular malformations.
authors.affiliation: Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey.
authors.forename: Leyla
authors.initials: L
authors.lastname: Sati
authors.affiliation: Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Zeiss
authors.affiliation: Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Yekkala
authors.affiliation: Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Demir
authors.affiliation: Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA james.mcgrath@yale.edu.
authors.forename: James
authors.initials: J
authors.lastname: McGrath
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C499208:Ctcfl protein, mouse; D004268:DNA-Binding Proteins; D016212:Transforming Growth Factor beta