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FXS is a neurodevelopmental disability characterized by intellectual impairment, seizures, autistic behavior, anxiety, and obesity. Here, we analyzed body weight as a function of mouse age, diet, and genotype to determine the effect of diet (soy, casein, and grain-based) on weight gain. We also assessed plasma protein biomarker expression and behavior in response to diet. Juvenile Fmr1KO mice fed a soy protein-based rodent chow throughout gestation and postnatal development exhibit increased weight gain compared to mice fed a casein-based purified ingredient diet or grain-based, low phytoestrogen chow. Adolescent and adult Fmr1KO mice fed a soy-based infant formula diet exhibited increased weight gain compared to reference diets. Increased body mass was due to increased lean mass. Wild-type male mice fed soy-based infant formula exhibited increased learning in a passive avoidance paradigm, and Fmr1KO male mice had a deficit in nest building. Thus, at the systems level, consumption of soy-based diets increases weight gain and affects behavior. At the molecular level, a soy-based infant formula diet was associated with altered expression of numerous plasma proteins, including the adipose hormone leptin and the \u03b2-amyloid degrading enzyme neprilysin. In conclusion, single-source, soy-based diets may contribute to the development of obesity and the exacerbation of neurological phenotypes in developmental disabilities, such as FXS.<\/jats:p>","DOI":"10.3390\/cells11081350","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T07:42:41Z","timestamp":1650094961000},"page":"1350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effects of Soy-Based Infant Formula on Weight Gain and Neurodevelopment in an Autism Mouse Model"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3919-3279","authenticated-orcid":false,"given":"Cara J.","family":"Westmark","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Wisconsin, Madison, WI 53706, USA"},{"name":"Molecular Environmental Toxicology Center, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikolaj J.","family":"Filon","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Wisconsin, Madison, WI 53706, USA"},{"name":"Undergraduate Research Program, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Maina","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Wisconsin, Madison, WI 53706, USA"},{"name":"Molecular Environmental Toxicology Summer Research Opportunities Program, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren I.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Wisconsin, Madison, WI 53706, USA"},{"name":"Undergraduate Research Program, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-226X","authenticated-orcid":false,"given":"Chrysanthy","family":"Ikonomidou","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela R.","family":"Westmark","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","unstructured":"Hales, C.M., Carroll, M.D., Fryar, C.D., and Ogden, C.L. 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