Neurosciences Graduate Program, University of California San Diego1, La Jolla, CA, United States of America.
Department of Psychiatry, University of California San Diego, La Jolla, CA, United States of America.
PLoS One. 2023 May 19;18(5):e0277446. doi: 10.1371/journal.pone.0277446. eCollection 2023.
Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near PTPRD as genome-wide significant, or strongly suggestive for this trait. We assessed Ptprd wild-type (WT), heterozygous (HT), and knockout (KO) mice for behavioral dimensions that are altered in OCD, including anxiety and exploration (open field test, dig test), perseverative behavior (splash-induced grooming, spatial d), sensorimotor gating (prepulse inhibition), and home cage goal-directed behavior (nest building). No effect of genotype was observed in any measure of the open field test, dig test, or splash test. However, Ptprd KO mice of both sexes showed impairments in nest building behavior. Finally, female, but not male, Ptprd KO mice showed deficits in prepulse inhibition, an operational measure of sensorimotor gating that is reduced in female, but not male, OCD patients. Our results indicate that constitutive lack of Ptprd may contribute to the development of certain domains that are altered OCD, including goal-directed behavior, and reduced sensorimotor gating specifically in females.
蛋白酪氨酸磷酸酯酶受体 D（PTPRD）是蛋白酪氨酸磷酸酯酶家族的成员，介导细胞黏附和突触特化。遗传研究将 Ptprd 与几种神经精神表型联系起来，包括不宁腿综合征（RLS）、阿片类药物滥用障碍和抗精神病药引起的体重增加。儿科强迫症特征或强迫症（OCD）的全基因组关联研究（GWAS）已经确定 PTPRD 附近的基因座是全基因组显著的，或者对这种特征有强烈的提示作用。我们评估了 Ptprd 野生型（WT）、杂合型（HT）和敲除（KO）小鼠在 OCD 中改变的行为维度，包括焦虑和探索（旷场试验、挖掘试验）、坚持性行为（飞溅诱导梳理、空间辨别）、感觉运动门控（预备脉冲抑制）和家庭笼中目标导向行为（筑巢）。在旷场试验、挖掘试验或飞溅试验的任何测量中，基因型都没有影响。然而，雄性和雌性 Ptprd KO 小鼠在筑巢行为方面都存在障碍。最后，雌性而非雄性 Ptprd KO 小鼠在 prepulse 抑制方面存在缺陷，这是一种感觉运动门控的操作性测量，在女性而非男性 OCD 患者中减少。我们的结果表明，PTPRD 的组成性缺乏可能导致 OCD 改变的某些领域的发展，包括目标导向行为，以及女性特异性的感觉运动门控降低。
