| First Author | Sperry ED | Year | 2014 |
| Journal | Dev Dyn | Volume | 243 |
| Issue | 9 | Pages | 1055-66 |
| PubMed ID | 24975120 | Mgi Jnum | J:214965 |
| Mgi Id | MGI:5604303 | Doi | 10.1002/dvdy.24156 |
| Citation | Sperry ED, et al. (2014) The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary for proper craniofacial and tracheal development. Dev Dyn 243(9):1055-66 |
| abstractText | BACKGROUND: Heterozygous mutations in the chromatin remodeling gene CHD7 cause CHARGE syndrome, a developmental disorder with variable craniofacial dysmorphisms and respiratory difficulties. The molecular etiologies of these malformations are not well understood. Homozygous Chd7 null mice die by E11, whereas Chd7(Gt/+) heterozygous null mice are a viable and excellent model of CHARGE. We explored skeletal phenotypes in Chd7(Gt/+) and Chd7 conditional knockout mice, using Foxg1-Cre to delete Chd7 (Foxg1-CKO) in the developing eye, ear, nose, pharyngeal pouch, forebrain, and gut and Wnt1-Cre (Wnt1-CKO) to delete Chd7 in migrating neural crest cells. RESULTS: Foxg1-CKO mice exhibited postnatal respiratory distress and death, dysplasia of the eye, concha, and frontal bone, hypoplastic maxillary shelves and nasal epithelia, and reduced tracheal rings. Wnt1-CKO mice exhibited frontal and occipital bone dysplasia, hypoplasia of the maxillary shelves and mandible, and cleft palate. In contrast, heterozygous Chd7(Gt/+) mice had apparently normal skeletal development. CONCLUSIONS: Conditional deletion of Chd7 in ectodermal and endodermal derivatives (Foxg1-Cre) or migrating neural crest cells (Wnt1-Cre) results in varied and more severe craniofacial defects than in Chd7(Gt/+) mice. These studies indicate that CHD7 has an important, dosage-dependent role in development of several different craniofacial tissues. |
