Abstract
Neural tube defects, mostly believed to result from closure defects of the neural tube during embryonic development, are frequently observed congenital malformations in humans. Since the etiology of these defects is not well understood yet, many animal models for neural tube defects, either arising from spontaneous mutations or generated by gene targeting, are being studied. The Bent tail mouse is a model for X-linked neural tube defects. This mutant has a characteristic short and kinked tail. Exencephaly occurs in Bent tail embryos with a frequency of 11–16%. Laterality defects also belong to the phenotypic spectrum. In this study, we analyzed the embryonic phenotype in further detail using scanning electron microscopy during the stages of neurulation. We observed a number of defects in both wild type and Bent tail embryos, including a kinked neural tube, tight amnion, delay in axial rotation and even malrotation. The severity or frequency of most defects, the delay in axial rotation excluded, was significantly higher in Bent tail embryos compared to wild type embryos. Other abnormalities were seen in Bent tail embryos only. These defects were related to anterior and posterior neural tube closure and resulted in exencephaly and a closure delay of the posterior neuropore, respectively. The exencephalic phenotype was further analyzed by light microscopy in ED14 embryos, showing disorganization and overgrowth in the mesencephalon and rhombencephalon. In conclusion, the anterior and posterior neural tube closure defects in the Bent tail are strictly linked to the genetic defect in this mouse. Other phenotypic features described in this study also occur in the wild type genetic background of the Bent tail strain. Apparently, the genetic background contains elements conducive to these developmental abnormalities.
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Acknowledgements
We thank Wiljan Wilms, Bianca Lemmers and Iris Elemans for providing care for the Bent tail mice, Dr. C.E.E.M. van der Zee for her help with the phenotype analysis, Mascha Schijvenaars for technical assistance, Hans Rensema for processing the SEM images and Dr. Carolien de Kovel for statistical analysis. Furthermore we would like to thank our colleagues for inspiring discussions at the NTD Symposium in Charleston, May 2002, and Dr. Madeleine Brouns for critically reading the manuscript. This study was supported by the Dutch Prinses Beatrix Fonds, grant 00-0208, and by the Dutch Organization for Scientific Research (ZonMW), grant 925-01-006.
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Franke, B., Klootwijk, R., Hekking, J.W.M. et al. Analysis of the embryonic phenotype of Bent tail, a mouse model for X-linked neural tube defects. Anat Embryol 207, 255–262 (2003). https://doi.org/10.1007/s00429-003-0345-2
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DOI: https://doi.org/10.1007/s00429-003-0345-2