Expression of the CTCFL Gene during Mouse Embryogenesis Causes Growth Retardation, Postnatal Lethality, and Dysregulation of the Transforming Growth Factor ß Pathway.
Mol Cell Biol
; 35(19): 3436-45, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26169830
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 ß (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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
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Proteínas de Ligação a DNA
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Retardo do Crescimento Fetal
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article