Tfap2b mutation in mice results in patent ductus arteriosus and renal malformation

Abstract

Background: Transcription factor TFAP2B is associated with Char syndrome in humans and is characterized by patent ductus arteriosus (PDA) and facial and finger abnormalities. In a previous study, we detected a c.435_438delCCGG TFAP2B mutation in a family with PDA, and no facial dysmorphism or finger abnormalities were observed. This 4-base pair (bp) deletion in exon 2 resulted in a truncated protein of about 21 kDa in cultured cells in vitro. However, it is not clear why c.435_438delCCGG mutation carriers are present with isolated PDA instead of Char syndrome.

Materials and methods: We successfully established a mouse model bearing Tfap2b c.435_438delCCGG mutation using CRISPR/Cas9 technology. The mutant mice were phenotyped using histological analysis, and the development of ductus smooth muscles in mutant mice was examined by immunohistochemistry.

Results: The c.435_438delCCGG homozygous mutant mice were characterized by delayed closure of the ductus arteriosus (DA) and renal malformation. Furthermore, the c.435_438delCCGG mutation might result in PDA by affecting the development of ductus arterious smooth muscle cells.

Conclusions: Using the c.435_438delCCGG homozygous mice, we verified the nature of the c.435_438delCCGG mutation and established a new and useful animal model to explore the function of Tfap2b and the mechanisms of PDA and renal formation. These findings may be useful for the development of therapies for those rare disorder.

Keywords: Frameshift mutation; Patent ductus arteriosus; Renal formation; Transcription factor Tfap2b.