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bioRxiv · 10.1101/2023.12.25.573296

Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring

Andruszewski, D.·Schelmbauer, C.·Uhlfelder, D. C.·Blanfeld, M.·Scherer, L.·Radyushkin, K.·Waisman, A.·Mufazalov, I. A.
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Abstract

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-17As 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 IL-17A transfer across the placental barrier and subsequent 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.

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Andruszewski, D., Schelmbauer, C., Uhlfelder, D. C., Blanfeld, M., Scherer, L., Radyushkin, K., Waisman, A., Mufazalov, I. A.. 2023-12-25. Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring. https://doi.org/10.1101/2023.12.25.573296

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