title: Autism-relevant behaviors are minimally impacted by conditional deletion of Pten in oxytocinergic neurons.
abstract: Germline heterozygous mutations in Pten (phosphatase and tensin homolog) are associated with macrocephaly and autism spectrum disorders (ASD). Pten germline heterozygous (Pten+/-) mice approximate these mutations, and both sexes show widespread brain overgrowth and impaired social behavior. Strikingly similar behavior phenotypes have been reported in oxytocin (Oxt) and/or oxytocin receptor (OxtR) knockout mice. Thus, we hypothesized that the behavioral phenotypes of germline Pten+/-mice may be caused by reduced Pten function in Oxt-expressing cells. To investigate this, we tested mice in which Pten was conditionally deleted using oxytocin-Cre (Oxt-Cre+; PtenloxP/+, Oxt-Cre+; PtenloxP/loxP) on a battery including assays of social, repetitive, depression-like, and anxiety-like behaviors. Minimal behavioral abnormalities were found; decreased anxiety-like behavior in the open field test in Oxt-Cre+; PtenloxP/loxPmales was the only result that phenocopied germline Pten+/-mice. However, Oxt cell size was dramatically increased in Oxt-Cre+; PtenloxP/loxPmice in adulthood. Thus, conditional deletion of Pten using Oxt-Cre has a profound effect on Oxt cell structure, but not on ASD-relevant behavior. We interpret these results as inconsistent with our starting hypothesis that reduced Pten function in Oxt-expressing cells causes the behavioral deficits observed in germline Pten+/-mice. Autism Res 2016, 9: 1248-1262. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
authors.affiliation: Department of Neuroscience, Scripps Research Institute, Jupiter, Florida.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Clipperton-Allen
authors.affiliation: Department of Neuroscience, Scripps Research Institute, Jupiter, Florida.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neuroscience, Scripps Research Institute, Jupiter, Florida.
authors.forename: Damon T
authors.initials: DT
authors.lastname: Page
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology; D001522:Behavior, Animal; D001921:Brain / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons; D010121:Oxytocin / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype
chemical_list: D010121:Oxytocin; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: anxiety-like behavior; autism spectrum disorder; hypertrophy; oxytocin; phosphatase and tensin homolog; social behavior