Use of high‐frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc‐deficient mice. (17th February 2017)

• Record Type: Journal Article
• Authors: Autuori, Maria C.; Pai, Yun J.; Stuckey, Daniel J.; Savery, Dawn; Marconi, Anna M.; Massa, Valentina; Lythgoe, Mark F.; Copp, Andrew J.; David, Anna L.; Greene, Nicholas D.E.
• Is Part Of: Prenatal diagnosis. Volume 37:Number 3(2017)
• Page Start: 273
• Page End: 281
• Publication Date: 2017-02-17
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.5004
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: 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). Method: 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. Results: 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. Conclusion: 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. Abstract : What's already known about this topic? 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 does this study add? 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.