title: Behavioral abnormalities in mice lacking mesenchyme-specific Pten.
abstract: Phosphatase and tensin homolog (Pten) is a negative regulator of cell proliferation and growth. Using a Cre-recombinase approach with Lox sequences flanking the fibroblast-specific protein 1 (Fsp1 aka S100A4; a mesenchymal marker), we probed sites of expression using a β-galactosidase Rosa26(LoxP) reporter allele; the transgene driving deletion of Pten (exons 4-5) was found throughout the brain parenchyma and pituitary, suggesting that deletion of Pten in Fsp1-positive cells may influence behavior. Because CNS-specific deletion of Pten influences social and anxiety-like behaviors and S100A4 is expressed in astrocytes, we predicted that loss of Pten in Fsp1-expressing cells would result in deficits in social interaction and increased anxiety. We further predicted that environmental enrichment would compensate for genetic deficits in these behaviors. We conducted a battery of behavioral assays on Fsp1-Cre;Pten(LoxP/LoxP) male and female homozygous knockouts (Pten(-/-)) and compared their behavior to Pten(LoxP/LoxP) (Pten(+/+)) conspecifics. Despite extensive physical differences (including reduced hippocampal size) and deficits in sensorimotor function, Pten(-/-) mice behaved remarkably similar to control mice on nearly all behavioral tasks. These results suggest that the social and anxiety-like phenotypes observed in CNS-specific Pten(-/-) mice may depend on neuronal Pten, as lack of Pten in Fsp1-expressing cells of the CNS had little effect on these behaviors.
authors.affiliation: Department of Neuroscience and the Behavioral Neuroendocrinology Group, The Ohio State University-Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: Jeremy.Borniger@osumc.edu.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Borniger
authors.affiliation: Department of Neuroscience and the Behavioral Neuroendocrinology Group, The Ohio State University-Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Yasmine M
authors.initials: YM
authors.lastname: Cissé
authors.affiliation: Department of Neuroscience and the Behavioral Neuroendocrinology Group, The Ohio State University-Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Carmen Z
authors.initials: CZ
authors.lastname: Cantemir-Stone
authors.affiliation: Comparative Pathology and Mouse Phenotyping Shared Resource. Comprehensive Cancer Center, The Ohio State University-Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Bolon
authors.affiliation: Department of Neuroscience and the Behavioral Neuroendocrinology Group, The Ohio State University-Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Nelson
authors.affiliation: Department of Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University-Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Clay B
authors.initials: CB
authors.lastname: Marsh
mesh_terms: D000374:Aggression / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001835:Body Weight / Q000235:genetics; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D001523:Mental Disorders / Q000235:genetics* / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D053580:Muscle Strength / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics; D021641:Recognition, Psychology / Q000502:physiology; D012021:Reflex, Abnormal / Q000235:genetics; D045442:Rotarod Performance Test; D000071999:S100 Calcium-Binding Protein A4 / Q000235:genetics / Q000378:metabolism; D012919:Social Behavior
chemical_list: D000071999:S100 Calcium-Binding Protein A4; C470944:S100a4 protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Astrocytes; Behavior; FSP1; Hippocampus; Pten; S100A4