title: Inactivation of the catalytic phosphatase domain of PTPRT/RPTPρ increases social interaction in mice.
abstract: Receptor protein tyrosine phosphatase rho (RPTPρ, gene symbol PTPRT) is a transmembrane protein expressed at high levels in the developing hippocampus, olfactory bulb, cortex, and cerebellum. It has an extracellular domain that interacts with other cell adhesion molecules, and it has two intracellular phosphatase domains, one of which is catalytically active. In a recent genome-wide association study, PTPRT was identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. Mutation of a critical aspartate to alanine (D1046A) in the PTPRT catalytic domain inactivates phosphatase function but retains substrate binding. We have generated a knockin mouse line carrying the PTPRT D1046A mutation. The D1046A mutation in homozygous knockin mice did not significantly change locomotor activities or anxiety-related behaviors. In contrast, male homozygous mice had significantly higher social approach scores than wild-type animals. Our results suggest that PTPRT phosphatase function is important in modulating neural pathways involved in mouse social behaviors relevant to the symptoms in human ASD patients.
authors.affiliation: Department of Pharmacology, The Ohio State University, Columbus, Ohio; Neuroscience Graduate Studies Program, The Ohio State University, Columbus, Ohio.
authors.forename: Keerthi
authors.initials: K
authors.lastname: Thirtamara Rajamani
authors.forename: Brian
authors.initials: B
authors.lastname: O'Neill
authors.forename: Dawn D
authors.initials: DD
authors.lastname: Han
authors.forename: Adrienne
authors.initials: A
authors.lastname: Frostholm
authors.forename: Andrej
authors.initials: A
authors.lastname: Rotter
authors.forename: Howard H
authors.initials: HH
authors.lastname: Gu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D009154:Mutation; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics*; D012737:Sex Factors
chemical_list: C516866:Ptprt protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: PTPRT; RPTPρ; animal model; social interaction