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Inactivation of the Catalytic Phosphatase Domain of PTPRT/RPTPρ Increases Social Interaction in Mice
Author(s) -
Thirtamara Rajamani Keerthi,
O'Neill Brian,
Han Dawn D.,
Frostholm Adrienne,
Rotter Andrej,
Gu Howard H.
Publication year - 2015
Publication title -
autism research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.656
H-Index - 66
eISSN - 1939-3806
pISSN - 1939-3792
DOI - 10.1002/aur.1390
Subject(s) - biology , phosphatase , mutation , microbiology and biotechnology , transmembrane domain , protein tyrosine phosphatase , genetics , receptor , gene , phosphorylation
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 ( D 1046 A ) in the PTPRT catalytic domain inactivates phosphatase function but retains substrate binding. We have generated a knockin mouse line carrying the PTPRT D 1046 A mutation. The D 1046 A 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. Autism Res 2015, 8: 19–28 . © 2014 International Society for Autism Research, Wiley Periodicals, Inc.