title: Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.
abstract: Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits.
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.|State Key Laboratory for Cognitive and Brain Sciences, The University of Hong Kong, Hong Kong SAR, China.|HKU-SIRI, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR, China. sychan@hku.hk.
authors.forename: Siu Yuen
authors.initials: SY
authors.lastname: Chan
authors.affiliation: Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kwun K
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wei
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yu On
authors.initials: YO
authors.lastname: Leung
authors.affiliation: Medical Physics and Research Department, Hong Kong Sanatorium and Hospital, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Abby Y
authors.initials: AY
authors.lastname: Ding
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Tomy C K
authors.initials: TC
authors.lastname: Hui
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Charlton
authors.initials: C
authors.lastname: Cheung
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Siew E
authors.initials: SE
authors.lastname: Chua
authors.affiliation: Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.|State Key Laboratory for Cognitive and Brain Sciences, The University of Hong Kong, Hong Kong SAR, China.|Genome Research Centre, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China.|Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Ed X
authors.initials: EX
authors.lastname: Wu
authors.affiliation: Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK. grainne.mcalonan@kcl.ac.uk.
authors.forename: Grainne M
authors.initials: GM
authors.lastname: McAlonan
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000002:abnormalities* / Q000254:growth & development*; D018797:Cell Cycle Proteins; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D007398:Interpersonal Relations; D008279:Magnetic Resonance Imaging; D008297:Male; D018345:Mice, Knockout; D009043:Motor Activity; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D065808:Prepulse Inhibition; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; C486649:DXBwg1396e protein, mouse; D009687:Nuclear Proteins; D012965:Sodium Chloride; D000661:Amphetamine
keywords: Lateral ventricles; Locomotion; MRI; Prepulse inhibition; Tspyl2
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