title: The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary for proper craniofacial and tracheal development.
abstract: 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.
authors: Department of Human Genetics, The University of Michigan, Ann Arbor, Michigan; The Medical School, The University of Michigan, Ann Arbor, Michigan; Medical Scientist Training Program, The University of Michigan, Ann Arbor, Michigan.
authors: Ethan D
authors: ED
authors: Sperry
authors: Elizabeth A
authors: EA
authors: Hurd
authors: Mark A
authors: MA
authors: Durham
authors: Elyse N
authors: EN
authors: Reamer
authors: Adam B
authors: AB
authors: Stein
authors: Donna M
authors: DM
authors: Martin
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D058747:CHARGE Syndrome / Q000235:genetics* / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D014132:Trachea / Q000002:abnormalities*
chemical_list: C507367:Chd7 protein, mouse; D004268:DNA-Binding Proteins
keywords: cleft palate; craniofacial disorders; skeletal dysplasia; trachea