Use of high-frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc-deficient mice.
Use of high-frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc-deficient mice.
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DOI：
10.1002/pd.5004
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发表时间：
2017-03
影响因子：
3
通讯作者：
Greene ND
中科院分区：
文献类型：
--
作者：
Autuori MC;Pai YJ;Stuckey DJ;Savery D;Marconi AM;Massa V;Lythgoe MF;Copp AJ;David AL;Greene ND
我们使用非侵入性高频超声(HFUS)成像技术在神经管缺陷(NTDS)和非酮症高血糖(NKH)小鼠模型中研究胚胎脑发育。利用高频超声，我们对携带编码甘氨酸脱羧酶的GLDC功能等位基因缺失的胚胎进行了成像，甘氨酸脱羧酶是线粒体叶酸代谢中甘氨酸裂解系统的一个组成部分，已知与人类颅骨NTDS和NKH有关。我们在胚胎发育的后半段连续检查了同一窝动物，并对大脑结构进行了量化。用聚合酶链式反应进行基因分型。组织学检查用于证实超声检查结果。高频超声可以在宫内检测GLDC缺陷小鼠胚胎中的两种主要脑部异常，即颅脑NTDS(脑外畸形)和脑室增大(与先前发现的出生后脑积水相对应)。连续超声波可以在连续的妊娠时间点对单个胚胎进行分析。从胚胎16.5天到18.5天，野生型和杂合子胚胎的侧脑室体积减小，而纯合子GLDC缺陷胚胎的侧脑室体积增加。HFUS在纯合子GLDC缺陷小鼠胚胎中检测到脑外畸形和脑室增大，这表明这是研究中枢神经系统发育的有效工具。对同一胚胎的纵向分析可以确定GLDC缺陷小鼠出生前脑室扩大的开始和进展。©2017作者。John Wiley&Sons，Ltd.发表的产前诊断。高频超声(HFUS)已被用于非侵入性监测孕中期(胚胎10.5-14.5天)宫内小鼠中枢神经系统(CNS)的发育；较晚的孕周仍有待研究。甘氨酸脱羧酶基因(GLDC)的错义突变在临床上与代谢紊乱、非酮症高血糖(NKH)和神经管畸形(NTDS)相关，如脑外畸形。关于这个话题，我们已经知道了些什么？我们将HFUS对小鼠中枢神经系统的成像延长到妊娠晚期胚胎18.5天，在该突变中缺乏GLDC，在该突变中NTDS，如脑外畸形和脑积水普遍存在。在此模型中，连续高频超声可以确定脑积水前脑室扩张的开始年龄。这项研究增加了什么？
We used non‐invasive high‐frequency ultrasound (HFUS) imaging to investigate embryonic brain development in a mouse model for neural tube defects (NTDs) and non‐ketotic hyperglycinemia (NKH). Using HFUS, we imaged embryos carrying loss of function alleles of Gldc encoding glycine decarboxylase, a component of the glycine cleavage system in mitochondrial folate metabolism, which is known to be associated with cranial NTDs and NKH in humans. We serially examined the same litter during the second half of embryonic development and quantified cerebral structures. Genotype was confirmed using PCR. Histology was used to confirm ultrasound findings. High‐frequency ultrasound allowed in utero detection of two major brain abnormalities in Gldc‐deficient mouse embryos, cranial NTDs (exencephaly) and ventriculomegaly (corresponding with the previous finding of post‐natal hydrocephalus). Serial ultrasound allowed individual embryos to be analysed at successive gestational time points. From embryonic day 16.5 to 18.5, the lateral ventricle volume reduced in wild‐type and heterozygous embryos but increased in homozygous Gldc‐deficient embryos. Exencephaly and ventriculomegaly were detectable by HFUS in homozygous Gldc‐deficient mouse embryos indicating this to be an effective tool to study CNS development. Longitudinal analysis of the same embryo allowed the prenatal onset and progression of ventricle enlargement in Gldc‐deficient mice to be determined. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. High‐frequency ultrasound (HFUS) has been used to non‐invasively monitor in utero mouse central nervous system (CNS) development during mid‐gestation (embryonic day 10.5–14.5); later gestational ages are yet to be studied. Missense mutations of the glycine decarboxylase gene (Gldc) are associated clinically with a metabolic disorder, Non‐ketotic hyperglycinemia (NKH) and neural tube defects (NTDs) such as exencephaly. What's already known about this topic? We extended HFUS imaging of the mouse CNS into late gestation embryonic day 18.5 in a genetic mouse mutant lacking Gldc in which NTDs, such as exencephaly, and hydrocephalus are prevalent. Serial HFUS can determine the age of onset of ventricle dilation that precedes hydrocephalus in this model. What does this study add?