Andruszewski David, Uhlfelder David C, Desiato Genni, Regen Tommy, Schelmbauer Carsten, Blanfeld Michaela, Scherer Lena, Radyushkin Konstantin, Pozzi Davide, Waisman Ari, Mufazalov Ilgiz A
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Research School of Translational Biomedicine (TransMed), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Mol Psychiatry. 2025 Apr;30(4):1585-1593. doi: 10.1038/s41380-024-02772-6. Epub 2024 Oct 10.
Prenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17A's action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated a transfer of transgenic IL-17A across the placental barrier, which triggered the development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.
产前对白介素17A（IL-17A）的印记会引发后代的行为障碍。然而，报道的利用免疫刺激剂的母体免疫激活模型缺乏特异性，无法阐明IL-17A作用的解剖学部位及其所导致的不同行为障碍。通过将转基因IL-17A过表达与母体中其受体的缺陷相结合，我们建立了一种新的对母体IL-17A产前印记的模型（首字母缩写：PRIMA-17模型）。该模型使我们能够研究仅通过胚胎限制性IL-17A反应建立的产前印记。我们证明了转基因IL-17A可穿过胎盘屏障，这引发了小鼠后代特定行为缺陷的发展。更具体地说，胚胎对IL-17A的反应导致早期生活中的交流障碍，这通过回巢检索叫声数量的减少来衡量。在成年期，IL-17A印记的后代表现出焦虑样行为增加。我们主张将我们的PRIMA-17模型作为研究小鼠神经缺陷的有用工具。
