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Alteration in the gene coding \u03b4-catenin has been implicated in many neurological disorders. Some of these genetic alterations exhibit a profound loss of \u03b4-catenin functions in excitatory synapses. We have shown that \u03b4-catenin deficiency induced by the homozygous \u03b4-catenin knockout (KO) and autism-associated missense glycine 34 to serine (G34S) mutation significantly alters AMPAR-mediated synaptic activity in cortical neurons and disrupts social behavior in mice. Importantly, many genetic disorders are caused by haploinsufficiency. Indeed, \u03b4-catenin haploinsufficiency contributes to severe autism and learning disabilities in humans. However, previous studies have used only homozygous \u03b4-catenin deficiency models. Therefore, it is important to examine the effects of \u03b4-catenin haploinsufficiency on animals\u2019 behaviors and excitatory synapses. Here, we use heterozygous \u03b4-catenin KO and G34S mice as a \u03b4-catenin haploinsufficiency model to examine this idea. Multiple behavioral assays, a social behavior test, contextual fear conditioning, and an open field test, reveal that both \u03b4-catenin KO and G34S haploinsufficiency significantly disrupt animals\u2019 social behavior and fear learning and memory. Interestingly, only KO haploinsufficiency mice show anxiety-like behavior. A biochemical assay using brain extracts demonstrates that \u03b4-catenin haploinsufficiency significantly affects the levels of synaptic \u03b4-catenin and AMPARs. Our findings thus suggest that \u03b4-catenin haploinsufficiency affects animals\u2019 behaviors via altering glutamatergic synaptic activity.<\/jats:p>","DOI":"10.1101\/2025.08.12.669907","type":"posted-content","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:55:18Z","timestamp":1755071718000},"source":"Crossref","is-referenced-by-count":1,"title":["\u03b4-catenin haploinsufficiency is sufficient to alter behaviors and glutamatergic synapses in mice"],"prefix":"10.64898","author":[{"given":"Emma S.","family":"Hinchliffe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Aragon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van T.","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapna A.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahmi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothi","family":"Arikkath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-2180","authenticated-orcid":false,"given":"Seonil","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025081420150643000_2025.08.12.669907v1.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1395-07.2007"},{"key":"2025081420150643000_2025.08.12.669907v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90353-0"},{"key":"2025081420150643000_2025.08.12.669907v1.3","first-page":"76","article-title":"Cadherins: key molecules for selective cell-cell adhesion","volume":"92","year":"1988","journal-title":"IARC Sci Publ"},{"key":"2025081420150643000_2025.08.12.669907v1.4","doi-asserted-by":"crossref","unstructured":"Gilbert J , Man HY . 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