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Cognitive impairments are observed in approximately 80% of children with this disease, with 45\u201360% exhibiting autism spectrum disorder (ASD) symptomatology. In light of the high comorbidity rate between ASD and NF1, we assessed early communicative behavior by maternal\u2010separation induced pup ultrasonic vocalizations (USV) and developmental milestones in two distinct <jats:italic>Nf1<\/jats:italic> genetically engineered models, one modeling clinical germline heterozygous loss of <jats:italic>Nf1<\/jats:italic> function (<jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice), and a second with somatic biallelic <jats:italic>Nf1<\/jats:italic> inactivation in neuroglial progenitor cells (<jats:italic>Nf1<\/jats:italic><jats:sup>GFAP<\/jats:sup>CKO mice). We observed altered USV production in both models: <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice exhibited both increased USVs across development and alterations in aspects of pitch, while <jats:italic>Nf1<\/jats:italic><jats:sup>GFAP<\/jats:sup>CKO mice demonstrated a decrease in USVs. Developmental milestones, such as weight, pinnae detachment, and eye opening, were not disrupted in either model, indicating the USV deficits were not due to gross developmental delay, and likely reflected more specific alterations in USV circuitry. In this respect, increased whole\u2010brain serotonin was observed in <jats:italic>Nf1<\/jats:italic><jats:sup>+\/\u2013<\/jats:sup> mice, but whole\u2010brain levels of dopamine and its metabolites were unchanged at the age of peak USV disruption, and USV alterations did not correlate with overall level of neurofibromin loss. The early communicative phenotypes reported herein should motivate further studies into the risks mediated by haploinsufficiency and biallelic deletion of <jats:italic>Nf1<\/jats:italic> across a full battery of ASD\u2010relevant behavioral phenotypes, and a targeted analysis of underlying circuitry disruptions. <jats:bold><jats:italic>Autism Res<\/jats:italic><\/jats:bold> <jats:italic>2018, 11: 44\u201358<\/jats:italic>. \u00a9 2017 International Society for Autism Research, Wiley Periodicals, Inc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder caused by mutation of the <jats:italic>NF1<\/jats:italic> gene, in which 80% of affected children exhibit cognitive and behavioral issues. Based on emerging evidence that NF1 may be an autism predisposition gene, we examined autism spectrum disorder (ASD)\u2010relevant early communicative behavior in <jats:italic>Nf1<\/jats:italic> mouse models and observed alterations in both models. The changes in early communicative behavior in <jats:italic>Nf1<\/jats:italic> mutant mice should motivate further studies into the causative factors and potential treatments for ASD arising in the context of NF1.<\/jats:p><\/jats:sec>","DOI":"10.1002\/aur.1853","type":"journal-article","created":{"date-parts":[[2017,8,26]],"date-time":"2017-08-26T05:42:38Z","timestamp":1503726158000},"page":"44-58","source":"Crossref","is-referenced-by-count":44,"title":["Characterization of early communicative behavior in mouse models of neurofibromatosis type 1"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5585-4722","authenticated-orcid":false,"given":"Susan E.","family":"Maloney","sequence":"first","affiliation":[{"name":"Department of Genetics Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"},{"name":"Department of Psychiatry Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystal C.","family":"Chandler","sequence":"additional","affiliation":[{"name":"Department of Genetics Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"},{"name":"Department of Psychiatry Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Anastasaki","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Rieger","sequence":"additional","affiliation":[{"name":"Department of Genetics Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"},{"name":"Department of Psychiatry Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Gutmann","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Dougherty","sequence":"additional","affiliation":[{"name":"Department of Genetics Washington University School of Medicine, 660 South Euclid Avenue St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00222716"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. 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