| RRC ID |
11797
|
| 著者 |
Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett AN, Vitelli F, Prescott K, Shaw-Smith C, Devriendt K, Bosman E, Steffes G, Steel KP, Simrick S, Basson MA, Illingworth E, Scambler PJ.
|
| タイトル |
Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice.
|
| ジャーナル |
J Clin Invest
|
| Abstract |
Aortic arch artery patterning defects account for approximately 20% of congenital cardiovascular malformations and are observed frequently in velocardiofacial syndrome (VCFS). In the current study, we screened for chromosome rearrangements in patients suspected of VCFS, but who lacked a 22q11 deletion or TBX1 mutation. One individual displayed hemizygous CHD7, which encodes a chromodomain protein. CHD7 haploinsufficiency is the major cause of coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, and ear anomalies/deafness (CHARGE) syndrome, but this patient lacked the major diagnostic features of coloboma and choanal atresia. Because a subset of CHARGE cases also display 22q11 deletions, we explored the embryological relationship between CHARGE and VCSF using mouse models. The hallmark of Tbx1 haploinsufficiency is hypo/aplasia of the fourth pharyngeal arch artery (PAA) at E10.5. Identical malformations were observed in Chd7 heterozygotes, with resulting aortic arch interruption at later stages. Other than Tbx1, Chd7 is the only gene reported to affect fourth PAA development by haploinsufficiency. Moreover, Tbx1+/-;Chd7+/- double heterozygotes demonstrated a synergistic interaction during fourth PAA, thymus, and ear morphogenesis. We could not rescue PAA morphogenesis by restoring neural crest Chd7 expression. Rather, biallelic expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal PAA development.
|
| 巻・号 |
119(11)
|
| ページ |
3301-10
|
| 公開日 |
2009-11-1
|
| DOI |
10.1172/JCI37561
|
| PII |
37561
|
| PMID |
19855134
|
| PMC |
PMC2769172
|
| MeSH |
Alleles*
Animals
Aorta, Thoracic / embryology*
Comparative Genomic Hybridization
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Ectoderm / metabolism*
Gene Expression Regulation, Developmental*
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
T-Box Domain Proteins / genetics
T-Box Domain Proteins / metabolism*
|
| IF |
11.864
|
| 引用数 |
78
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| リソース情報 |
| 実験動物マウス |
RBRC01145 |
