Perinatal nutrition interacts with genetic background to alter behavior in a parent‐of‐origin‐dependent manner in adult Collaborative Cross mice |
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| Authors: | S A Schoenrock D Oreper J Farrington R C McMullan R Ervin D R Miller F Pardo‐Manuel de Villena W Valdar L M Tarantino |
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| Affiliation: | 1. Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;2. Neuroscience Curriculum, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;3. Bioinformatics and Computational Biology Curriculum, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;4. Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;5. Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina;6. Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina |
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| Abstract: | Previous studies in animal models and humans have shown that exposure to nutritional deficiencies in the perinatal period increases the risk of psychiatric disease. Less well understood is how such effects are modulated by the combination of genetic background and parent‐of‐origin (PO). To explore this, we exposed female mice from 20 Collaborative Cross (CC) strains to protein deficient, vitamin D deficient, methyl donor enriched or standard diet during the perinatal period. These CC females were then crossed to a male from a different CC strain to produce reciprocal F1 hybrid females comprising 10 distinct genetic backgrounds. The adult F1 females were then tested in the open field, light/dark, stress‐induced hyperthermia, forced swim and restraint stress assays. Our experimental design allowed us to estimate effects of genetic background, perinatal diet, PO and their interactions on behavior. Genetic background significantly affected all assessed phenotypes. Perinatal diet exposure interacted with genetic background to affect body weight, basal body temperature, anxiety‐like behavior and stress response. In 8 of 9 genetic backgrounds, PO effects were observed on multiple phenotypes. Additionally, we identified a small number of diet‐by‐PO effects on body weight, stress response, anxiety‐ and depressive‐like behavior. Our data show that rodent behaviors that model psychiatric disorders are affected by genetic background, PO and perinatal diet, as well as interactions among these factors. |
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| Keywords: | anxiety depression development gene‐by‐environment methyl donors multi‐parental populations protein psychiatric disorders stress vitamin D |
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