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We examined indices of development and adult behaviour in a mouse model of\n                    <jats:italic>Setd1a<\/jats:italic>\n                    haploinsufficiency, revealing a complex pattern of sex-related differences spanning the pre- and post-natal period. Specifically, male\n                    <jats:italic>Setd1a<\/jats:italic>\n                    <jats:sup>+\/-<\/jats:sup>\n                    mice had smaller placentae at E11.5 and females at E18.5 without any apparent changes in foetal size. In contrast, young male\n                    <jats:italic>Setd1a<\/jats:italic>\n                    <jats:sup>+\/-<\/jats:sup>\n                    mice had lower body weight and showed enhanced growth, leading to equivalent weights by adulthood. Embryonic whole brain RNA-seq analysis revealed expression changes that were significantly enriched for mitochondria-related genes in\n                    <jats:italic>Setd1a<\/jats:italic>\n                    <jats:sup>+\/<\/jats:sup>\n                    samples. In adulthood, we found enhanced acoustic startle responding in male\n                    <jats:italic>Setd1a<\/jats:italic>\n                    <jats:sup>+\/-<\/jats:sup>\n                    mice which was insentitive to the effects of risperidone, but not haloperidol, both commonly used antipsychotic drugs. We also observed reduced pre-pulse inhibition of acoustic startle, a schizophrenia-relevant phenotype, in both male and female\n                    <jats:italic>Setd1a<\/jats:italic>\n                    <jats:sup>+\/-<\/jats:sup>\n                    mice which could not be rescued by either drug. In the open field and elevated plus maze tests of anxiety,\n                    <jats:italic>Setd1a<\/jats:italic>\n                    haplosufficiency led to more anxiogenic behaviour in both sexes, whereas there were no differences in general motoric ability and memory. Thus, we find evidence for changes in a number of phenotypes which strengthen the support for the use of\n                    <jats:italic>Setd1a<\/jats:italic>\n                    haploinsufficient mice as a model for the biological basis of schizophrenia. Furthermore, our data point towards possible underpinning neural and developmental mechanisms that may be subtly different between the sexes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0298717","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T13:33:53Z","timestamp":1723642433000},"page":"e0298717","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex-dependent effects of Setd1a haploinsufficiency on development and adult behaviour"],"prefix":"10.1371","volume":"19","author":[{"given":"Matthew L.","family":"Bosworth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-5712","authenticated-orcid":true,"given":"Anthony R.","family":"Isles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence 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