Vogt Daniel, Cho Kathleen K A, Lee Anthony T, Sohal Vikaas S, Rubenstein John L R
Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA; Nina Ireland Laboratory of Developmental Neurobiology, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA; Sloan-Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell Rep. 2015 May 12;11(6):944-956. doi: 10.1016/j.celrep.2015.04.019. Epub 2015 Apr 30.
Mutations in the phosphatase PTEN are strongly implicated in autism spectrum disorder (ASD). Here, we investigate the function of Pten in cortical GABAergic neurons using conditional mutagenesis in mice. Loss of Pten results in a preferential loss of SST(+) interneurons, which increases the ratio of parvalbumin/somatostatin (PV/SST) interneurons, ectopic PV(+) projections in layer I, and inhibition onto glutamatergic cortical neurons. Pten mutant mice exhibit deficits in social behavior and changes in electroencephalogram (EEG) power. Using medial ganglionic eminence (MGE) transplantation, we test for cell-autonomous functional differences between human PTEN wild-type (WT) and ASD alleles. The PTEN ASD alleles are hypomorphic in regulating cell size and the PV/SST ratio in comparison to WT PTEN. This MGE transplantation/complementation assay is efficient and is generally applicable for functional testing of ASD alleles in vivo.
磷酸酶PTEN的突变与自闭症谱系障碍（ASD）密切相关。在此，我们利用小鼠的条件性诱变来研究Pten在皮质GABA能神经元中的功能。Pten的缺失导致SST(+)中间神经元优先丢失，这增加了小白蛋白/生长抑素（PV/SST）中间神经元的比例、I层中异位的PV(+)投射以及对谷氨酸能皮质神经元的抑制作用。Pten突变小鼠表现出社交行为缺陷和脑电图（EEG）功率变化。利用内侧神经节隆起（MGE）移植，我们测试了人类PTEN野生型（WT）和ASD等位基因之间的细胞自主功能差异。与WT PTEN相比，PTEN ASD等位基因在调节细胞大小和PV/SST比例方面功能减退。这种MGE移植/互补分析是有效的，并且普遍适用于体内ASD等位基因的功能测试。
