title: Use of high-frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc-deficient mice.
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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Newlife Birth Defects Research Centre and Developmental Biology and Cancer Programme, Great Ormond Street Institute of Child Health, University College London, London, UK.|Department of Obstetrics and Gynaecology, San Paolo Hospital, Milan, Italy.
authors.forename: Maria C
authors.identifier: http://orcid.org/0000-0003-4107-325X
authors.initials: MC
authors.lastname: Autuori
authors.affiliation: Newlife Birth Defects Research Centre and Developmental Biology and Cancer Programme, Great Ormond Street Institute of Child Health, University College London, London, UK.
authors.forename: Yun J
authors.identifier: http://orcid.org/0000-0001-7016-8667
authors.initials: YJ
authors.lastname: Pai
authors.affiliation: Centre for Advanced Biomedical Imaging, University College London, London, UK.
authors.forename: Daniel J
authors.identifier: http://orcid.org/0000-0001-8888-627X
authors.initials: DJ
authors.lastname: Stuckey
authors.affiliation: Newlife Birth Defects Research Centre and Developmental Biology and Cancer Programme, Great Ormond Street Institute of Child Health, University College London, London, UK.
authors.forename: Dawn
authors.initials: D
authors.lastname: Savery
authors.affiliation: Department of Obstetrics and Gynaecology, San Paolo Hospital, Milan, Italy.
authors.forename: Anna M
authors.identifier: http://orcid.org/0000-0001-6295-1854
authors.initials: AM
authors.lastname: Marconi
authors.affiliation: Department of Health Science, San Paolo Hospital, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Massa
authors.affiliation: Centre for Advanced Biomedical Imaging, University College London, London, UK.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.affiliation: Newlife Birth Defects Research Centre and Developmental Biology and Cancer Programme, Great Ormond Street Institute of Child Health, University College London, London, UK.
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0002-2544-9117
authors.initials: AJ
authors.lastname: Copp
authors.affiliation: Maternal and Fetal Medicine, Institute for Women's Health, University College London, London, UK.
authors.forename: Anna L
authors.identifier: http://orcid.org/0000-0002-0199-6140
authors.initials: AL
authors.lastname: David
authors.affiliation: Newlife Birth Defects Research Centre and Developmental Biology and Cancer Programme, Great Ormond Street Institute of Child Health, University College London, London, UK.
authors.forename: Nicholas D E
authors.identifier: http://orcid.org/0000-0002-4170-5248
authors.initials: ND
authors.lastname: Greene
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000000981:diagnostic imaging / Q000196:embryology; D004622:Embryo, Mammalian; D005260:Female; D050841:Glycine Dehydrogenase (Decarboxylating) / Q000235:genetics*; D006849:Hydrocephalus / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D011247:Pregnancy; D012886:Skull / Q000000981:diagnostic imaging / Q000196:embryology; D016216:Ultrasonography, Prenatal / Q000379:methods
chemical_list: D050841:Glycine Dehydrogenase (Decarboxylating)