McQuinn T C, Miga D E, Mjaatvedt C H, Phelps A L, Wessels A
Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, Charleston, South Carolina, USA.
Anat Rec. 2001 May 1;263(1):62-71. doi: 10.1002/ar.1077.
The inv/inv mouse carries an insertional mutation in the inversin gene, (inv, for inversion of embryonic turning). Previously it had been reported that almost 100% of the homozygous offspring (inv/inv) were characterized by situs inversus totalis. In this report we identify the spectrum of cardiopulmonary anatomical abnormalities in inv/inv mice surviving to birth to determine whether the abnormalities seen are of the categories classically associated with human situs abnormalities. Stillborn mice, offspring that died unexpectedly (within 48 hr after birth), and neonates with phenotypic characteristics of situs inversus (right-sided stomachs, growth failure or jaundice) were processed for standard histological examination. Of 173 offspring, 34 (20%) neonates (11 stillborn, 9 unexpected deaths, and 14 mice with situs inversus phenotype) were examined, 27 of which were genotyped to be inv/inv. Interestingly, three inv/inv mice (11%) were found to have situs solitus. Twenty-four had situs inversus with normal, mirror-image cardiac anatomy (dextrocardia with atrioventricular concordance, ventriculoarterial concordance and a right aortic arch). The overall incidence of cardiovascular anomalies observed was 10 out of 27 (37%). The most frequent severe malformation, identified in 3 out of 27 animals, was a complex consisting of pulmonary infundibular stenosis/atresia with absence of pulmonary valve tissue and a ventricular septal defect. The pulmonary phenotype in inv/inv mice was situs inversus with occasional minor lobar abnormalities. We conclude that 1) cardiopulmonary malformations in inv/inv mice are not rare (37%), 2) the cardiopulmonary malformations observed in inv/inv specimens are not of the spectrum typically associated with human heterotaxia. In particular, inv/inv mice have a propensity for defects in the development of the right ventricular outflow tract and the interventricular septum, and 3) approximately one out of ten inv/inv mice is born with situs solitus and shows cardiac anomalies that correspond to those observed in inv/inv specimens with situs inversus. Our data therefore suggest that inversin, the product of the inv locus, may have specific roles in cardiac morphogenesis independent of its role in situs determination.
inv/inv小鼠在inversin基因中携带插入突变（inv，代表胚胎旋转反转）。此前有报道称，几乎100%的纯合后代（inv/inv）表现为完全性内脏反位。在本报告中，我们鉴定了存活至出生的inv/inv小鼠心肺解剖异常的范围，以确定所观察到的异常是否属于与人类内脏位置异常经典相关的类别。对死产小鼠、意外死亡的后代（出生后48小时内）以及具有内脏反位表型特征（右侧胃、生长发育不良或黄疸）的新生儿进行标准组织学检查。在173只后代中，检查了34只（20%）新生儿（11只死产、9只意外死亡和14只具有内脏反位表型的小鼠），其中27只基因分型为inv/inv。有趣的是，发现3只inv/inv小鼠（11%）为正常内脏位置。24只具有内脏反位，心脏解剖结构正常且呈镜像（右位心，房室一致、心室动脉一致且有右主动脉弓）。观察到的心血管异常总发生率为27只中的10只（37%）。在27只动物中有3只发现的最常见严重畸形是一种复杂畸形，包括肺动脉漏斗部狭窄/闭锁且无肺动脉瓣组织以及室间隔缺损。inv/inv小鼠的肺部表型为内脏反位，偶尔有轻微叶异常。我们得出结论：1）inv/inv小鼠的心肺畸形并不罕见（37%）；2）在inv/inv标本中观察到的心肺畸形不属于通常与人类内脏异位相关的范围。特别是，inv/inv小鼠右心室流出道和室间隔发育有缺陷的倾向；3）大约十分之一的inv/inv小鼠出生时为正常内脏位置，并表现出与具有内脏反位的inv/inv标本中观察到的心脏异常相对应的心脏异常。因此，我们的数据表明，inv位点的产物inversin可能在心脏形态发生中具有独立于其在确定内脏位置方面作用的特定作用。
