Lindsay E A, Baldini A
Department of Pediatrics (Cardiology), Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Hum Mol Genet. 2001 Apr 15;10(9):997-1002. doi: 10.1093/hmg/10.9.997.
Chromosome 22q11.2 heterozygous deletions cause the most common deletion syndrome, including the DiGeorge syndrome phenotype. Using a mouse model of this deletion (named Df1) we show that the aortic arch patterning defects that occur in heterozygously deleted mice (Df1/+) are associated with a differentiation impairment of vascular smooth muscle in the 4th pharyngeal arch arteries (PAAs) during early embryogenesis. Using molecular markers for neural crest, endothelial cells and vascular smooth muscle, we show that cardiac neural crest migration into the 4th arch and initial formation of the 4th PAAs are apparently normal in Df1/+ embryos, but affected vessels are growth-impaired and do not acquire vascular smooth muscle. As in humans, not all deleted mice present with cardiovascular defects at birth. However, we found, unexpectedly, that all Df1/+ embryos have abnormally small 4th PAAs during early embryogenesis. Many embryos later overcome this early defect, coincident with the appearance of vascular smooth muscle differentiation, and develop normally. Embryos born with aortic arch patterning defects probably represent a more severely affected group that fails to attain sufficient 4th PAA growth for normal remodelling of the PAA system. Our data indicate that Df1/+ embryos are able to overcome a localized arterial growth impairment and thereby reduce the penetrance of birth defects.
22号染色体q11.2区域的杂合缺失会导致最常见的缺失综合征，包括迪格奥尔格综合征表型。利用这种缺失的小鼠模型（命名为Df1），我们发现杂合缺失小鼠（Df1/+）中出现的主动脉弓形态发生缺陷与胚胎早期发育过程中第四咽弓动脉（PAA）血管平滑肌的分化受损有关。使用神经嵴、内皮细胞和血管平滑肌的分子标记，我们发现心脏神经嵴向第四弓的迁移以及第四PAA的初始形成在Df1/+胚胎中显然是正常的，但受影响的血管生长受损且未获得血管平滑肌。与人类一样，并非所有缺失小鼠出生时都有心血管缺陷。然而，我们意外地发现，所有Df1/+胚胎在胚胎早期第四PAA都异常小。许多胚胎后来克服了这种早期缺陷，这与血管平滑肌分化的出现同时发生，并正常发育。出生时患有主动脉弓形态发生缺陷的胚胎可能代表了一个受影响更严重的群体，该群体未能实现第四PAA的充分生长以进行PAA系统的正常重塑。我们的数据表明，Df1/+胚胎能够克服局部动脉生长障碍，从而降低出生缺陷的外显率。
