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A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice.

Publication ,  Journal Article
Shi, F; Ding, S; Zhao, S; Han, M; Zhuang, Y; Xu, T; Wu, X
Published in: Hum Mol Genet
July 15, 2014

Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is an autosomal dominant genetic disorder characterized by small palpebral fissures and other craniofacial malformations, often with (type I) but could also without (type II) premature ovarian failure. While mutations of the forkhead transcription factor FOXL2 are associated with and likely be responsible for many BPES cases, how FOXL2 affects craniofacial development remain to be understood. Through a large-scale piggyBac (PB) insertion mutagenesis, we have identified a mouse mutant carrying a PB insertion ∼160 kb upstream of the transcription start site (TSS) of Foxl2. The insertion reduces, but not eliminates, the expression of Foxl2. This mutant, but not its revertant, displays BPES-like conditions such as midface hypoplasia, eyelid abnormalities and female subfertility. Further analysis indicates that the mutation does not affect mandible, but causes premature fusion of the premaxilla-maxilla suture, smaller premaxilla and malformed maxilla during midface development. We further identified an evolutionarily conserved fragment near the insertion site and observed enhancer activity of this element in tissue culture cells. Analyses using DNase I hypersensitivity assay and chromosome conformation capture assay in developing maxillary and periocular tissues suggest that the DNA region near the insertion site likely interacts with Foxl2 TSS. Therefore, this mutant presents an excellent animal model for mechanistic study of BPES and regulation of Foxl2.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

July 15, 2014

Volume

23

Issue

14

Start / End Page

3792 / 3800

Location

England

Related Subject Headings

  • Urogenital Abnormalities
  • Skin Abnormalities
  • Mutagenesis, Insertional
  • Mice
  • Maxilla
  • Humans
  • Genetics & Heredity
  • Forkhead Transcription Factors
  • Forkhead Box Protein L2
  • Disease Models, Animal
 

Citation

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Shi, F., Ding, S., Zhao, S., Han, M., Zhuang, Y., Xu, T., & Wu, X. (2014). A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice. Hum Mol Genet, 23(14), 3792–3800. https://doi.org/10.1093/hmg/ddu092
Shi, Fubiao, Sheng Ding, Shimin Zhao, Min Han, Yuan Zhuang, Tian Xu, and Xiaohui Wu. “A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice.Hum Mol Genet 23, no. 14 (July 15, 2014): 3792–3800. https://doi.org/10.1093/hmg/ddu092.
Shi F, Ding S, Zhao S, Han M, Zhuang Y, Xu T, et al. A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice. Hum Mol Genet. 2014 Jul 15;23(14):3792–800.
Shi, Fubiao, et al. “A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice.Hum Mol Genet, vol. 23, no. 14, July 2014, pp. 3792–800. Pubmed, doi:10.1093/hmg/ddu092.
Shi F, Ding S, Zhao S, Han M, Zhuang Y, Xu T, Wu X. A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice. Hum Mol Genet. 2014 Jul 15;23(14):3792–3800.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

July 15, 2014

Volume

23

Issue

14

Start / End Page

3792 / 3800

Location

England

Related Subject Headings

  • Urogenital Abnormalities
  • Skin Abnormalities
  • Mutagenesis, Insertional
  • Mice
  • Maxilla
  • Humans
  • Genetics & Heredity
  • Forkhead Transcription Factors
  • Forkhead Box Protein L2
  • Disease Models, Animal