Increased nuchal translucency origins from abnormal lymphatic development and is independent of the presence of a cardiac defect.
OBJECTIVE
To assess whether cardiac failure, because of cardiac defects, and abnormal jugular lymphatic development are involved in nuchal edema (NE) - the morphological equivalent of increased nuchal translucency - in various euploid mutant mouse models.


METHODS
Mouse embryos with lymphatic abnormalities and NE (Ccbe1(-/-)), with cardiac defects and NE (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+)) and with cardiac malformations without NE (Tbx2(-/-), Pitx2(-/-), Fgf10(-/-), Jarid2(-/-NE-)) were examined. Embryos were analyzed from embryonic day 11.5 to 15.5. Markers for lymphatic vessels, endothelium, smooth muscle cells and nerves were used to study the nuchal region. Hematoxylin-Azophloxine staining was performed to examine cardiac morphology.


RESULTS
Mouse embryos with lymphatic abnormalities and NE (Ccbe1(-/-)) showed no formation of the jugular lymphatic sac but normal cardiac morphology. In mouse embryos with cardiac defects and NE (Fkbp12(-/-), Tbx1(-/-), Chd7(fl/fl);Mesp1Cre, Jarid2(-/-NE+)) enlarged jugular lymphatic sacs or large nuchal cavities within the NE were found. In mouse embryos with a cardiac malformation without NE (Tbx2(-/-), Pitx2(-/-), Fgf10(-/-), Jarid2(-/-NE-)) normal jugular lymphatic sacs were observed.


CONCLUSIONS
NE consistently coincides with abnormal jugular lymphatic development in euploid mouse embryos, independent of cardiac anatomy. NE is unlikely to be caused by temporary cardiac failure solely because of a cardiac defect.
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Nicole B
NB
Burger
Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands.
Mireille N
MN
Bekker
Department of Anatomy, Embryology and Physiology, Academic Medical Center, Amsterdam, The Netherlands.
Evelien
E
Kok
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
Christianne J M
CJ
De Groot
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
James F
JF
Martin
Riley Heart Research Center, Division of Pediatric Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Weinian
W
Shou
Department of Molecular Medicine, UCL Institute of Child Health, London, United Kingdom.
Peter J
PJ
Scambler
Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA.
Youngsook
Y
Lee
Department of Anatomy, Embryology and Physiology, Academic Medical Center, Amsterdam, The Netherlands.
Vincent M
VM
Christoffels
Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
Monique C
MC
Haak
D000818:Animals; D005260:Female; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging*; D044148:Lymphatic Abnormalities / Q000000981:diagnostic imaging*; D018345:Mice, Knockout; D048208:Nuchal Translucency Measurement; D011247:Pregnancy