Expression of the CTCFL Gene during Mouse Embryogenesis Causes Growth Retardation, Postnatal Lethality, and Dysregulation of the Transforming Growth Factor β Pathway

CTCFL , a paralog ofCTCF , also known asBORIS (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 ofCtcfl , we created tetracycline-inducibleCtcfl transgenic mice. We show thatCtcfl 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 theCtcfl transgene reproduce the phenotype in ES cell-tetraploid chimeras. Transcriptome sequencing of theCtcfl ES cells revealed 14 genes deregulated byCtcfl expression. Bioinformatic analysis revealed the TGFB pathway as most affected by embryonicCtcfl expression. Understanding the consequence ofCtcfl expression in nontesticular cells and elucidating downstream targets ofCtcfl could explain the role of its product as a CTA and its involvement in two, if not more, human vascular malformations.