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. 2023 Jan 21;13:1215. doi: 10.1038/s41598-023-27782-2

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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R402H^mod/R402H^mod embryos show a severe neurodevelopmental phenotype which is not observed in R402H^wt/R402H^wt mice. (a–c) Representative coronal sections of E16.5 embryos stained with Nissl. Wild-type (+/+), heterozygous (R402H^wt/+) and homozygous (R402H^wt/R402H^wt) animals are indistinguishable. (a′–c′) Enlargements of the boxed areas marked in (a–c) showing no differences in cortical organization between genotypes. (d–f) Representative coronal sections of E16.5 embryos stained with Nissl of wild-type (+/+), heterozygous (R402H^mod/+) and homozygous (R402H^mod/R402H^mod) animals. Brain development is significantly impaired in homozygotes, leading to perinatal lethality. (d′–f′) Enlargements of the boxed areas marked in (d–f) showing a severe cortical disorganization in R402H^mod/R402H^mod embryos compared to littermates. Scale bars indicate 500 μm in (a) and (d), and 100 μm in (a′) and (d′).