Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24975120
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary
for proper craniofacial and tracheal development
#MMPMID24975120
Sperry ED
; Hurd EA
; Durham MA
; Reamer EN
; Stein AB
; Martin DM
Dev Dyn
2014[Sep]; 243
(9
): 1055-66
PMID24975120
show ga
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.
free
free
free
