- Title
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Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish
- Authors
- Siekierska, A., Stamberger, H., Deconinck, T., Oprescu, S.N., Partoens, M., Zhang, Y., Sourbron, J., Adriaenssens, E., Mullen, P., Wiencek, P., Hardies, K., Lee, J.S., Giong, H.K., Distelmaier, F., Elpeleg, O., Helbig, K.L., Hersh, J., Isikay, S., Jordan, E., Karaca, E., Kecskes, A., Lupski, J.R., Kovacs-Nagy, R., May, P., Narayanan, V., Pendziwiat, M., Ramsey, K., Rangasamy, S., Shinde, D.N., Spiegel, R., Timmerman, V., von Spiczak, S., Helbig, I., C4RCD Research Group, AR working group of the EuroEPINOMICS RES Consortium, Weckhuysen, S., Francklyn, C., Antonellis, A., de Witte, P., De Jonghe, P.
- Source
- Full text @ Nat. Commun.
vars−/− larvae display severe developmental phenotype with early lethality. a Spatiotemporal expression patterns of vars by whole-mount RNA in situ hybridization at 18, 24, 36, and 72 hpf. BA Branchial Arches; H Hindbrain; HICM Hematopoietic Intermediate Cell Mass; Ints Intestine; Liv Liver; MBH Midbrain-Hindbrain boundary; M Midbrain; R Retina. Scale bars = 200 μm b RT-qPCR data demonstrating the expression of total vars in vars+/+, vars+/−, and vars−/− larvae at 3 and 5 dpf. Values are mean of three separate experiments performed in triplicate. c Kaplan–Meier survival curve of vars+/+ (n = 37), vars+/− (n = 82), and vars−/− (n = 34) larvae. d Graph illustrating changes in loss-of-posture and touch response of vars−/−larvae throughout the life span. Only the surviving larvae were included. e Representative lateral and dorsal bright-field images of 3 and 5 dpf vars+/+, vars+/−, and vars−/− larvae (scale bar, 500 μm). Pericardial edema, small eye, and periocular swelling around the eye were marked with arrows. f H&E histological staining of paraffin-embedded coronary sections from the forebrain of 1–5 dpf vars+/+, vars+/−, and vars−/− larvae (scale bar, 100 μm). Magnification of the disruption in the organization of the brain and the eye for 5 dpf vars+/+, vars+/−, and vars−/− was marked with black and green stripped line, respectively. Red arrows point out some structural abnormalities. D diencephalon; IPL inner plexiform layer; L lens; MC mandibular cartilage; ON optic nerve; OPL outer plexiform layer; R&C rods and cones; RGC retinal ganglion cell; T trabecula. g–i Comparison of the individual measurements for head size g, brain size h, and eye size i for vars+/+, vars+/−, and vars−/− at 3 dpf (n = 9, n = 20 and n = 11, respectively) and 5 dpf (n = 9, n = 14 and n = 24, respectively). In b and g–i one-way ANOVA with Tukey’s multiple comparisons test was used. Values are mean of three separate experiments. In c log-rank (Mantel-Cox) test was used. Error bars represent SD. Significant values are noted as ***p < 0.001 and ****p < 0.0001 EXPRESSION / LABELING:
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ZFIN is incorporating published figure images and captions as part of an ongoing project. Figures from some publications have not yet been curated, or are not available for display because of copyright restrictions. |
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ZFIN is incorporating published figure images and captions as part of an ongoing project. Figures from some publications have not yet been curated, or are not available for display because of copyright restrictions. PHENOTYPE:
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ZFIN is incorporating published figure images and captions as part of an ongoing project. Figures from some publications have not yet been curated, or are not available for display because of copyright restrictions. |
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ZFIN is incorporating published figure images and captions as part of an ongoing project. Figures from some publications have not yet been curated, or are not available for display because of copyright restrictions. PHENOTYPE:
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ZFIN is incorporating published figure images and captions as part of an ongoing project. Figures from some publications have not yet been curated, or are not available for display because of copyright restrictions. PHENOTYPE:
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