SHANK3 is one of the scaffolding proteins in the postsynaptic density (PSD). Pain perception and underlying mechanisms were investigated in Shank3 exon 21 deficient (Shank3△C) mice. Sixty-six mice were attributed according to their genotype to three groups: (1) wild-type (WT), (2) heterozygous Shank3△C/+, and (3) homozygous Shank3△C/△C. Complete Freund's adjuvant (CFA) was used to induce inflammatory pain, and thermal hyperalgesia was determined. CFA treatment reduced the thermal threshold in the WT group; groups expressing mutations of Shank3 (△C/+ and △C/△C) had higher thresholds after CFA administration compared to the WT group. Mice with Shank3 mutations (△C/+ or △C/△C) had a lower expression of GluN2A and IP3R proteins and a higher expression of mGluR5 protein in the PSD compared to WT mice without changes in GluN1, GluN2B, and Homer expression. The crosslinking of Homer-IP3R, but not Homer-mGluR5, was decreased in the total lysate. Deficit of Shank3 exon 21 may lead to impaired perception of thermal pain in mice under inflammatory conditions. This impairment may result from protein dysregulation in the PSD like downregulation of the GluN2A subunit, which may reduce NMDAR-mediated currents, and/or decreased crosslinking between Homer and IP3R, which may reduce the release of Ca2+ from intracellular stores.

中文翻译：

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SHANK3 亚型的缺乏会损害热痛觉过敏和脊髓中突触后蛋白的表达失调

SHANK3 是突触后密度 (PSD) 中的支架蛋白之一。在 Shank3 外显子 21 缺陷 (Shank3△C) 小鼠中研究了疼痛感知和潜在机制。66只小鼠根据基因型分为三组：（1）野生型（WT），（2）杂合Shank3△C/+，和（3）纯合Shank3△C/△C。完全弗氏佐剂 (CFA) 用于诱导炎性疼痛，并测定热痛觉过敏。CFA 治疗降低了 WT 组的热阈值；与WT组相比，CFA给药后表达Shank3突变（△C/+和△C/△C）的组具有更高的阈值。与 GluN1、GluN2B、GluN1、GluN2B 没有变化的 WT 小鼠相比，具有 Shank3 突变（△C/+ 或 △C/△C）的小鼠在 PSD 中具有较低的 GluN2A 和 IP3R 蛋白表达和较高的 mGluR5 蛋白表达。和荷马的表达。Homer-IP3R 的交联在总裂解物中降低，但 Homer-mGluR5 没有降低。Shank3 外显子 21 的缺陷可能导致小鼠在炎症条件下对热痛的感知受损。这种损伤可能是由 PSD 中的蛋白质失调引起的，如 GluN2A 亚基的下调，这可能会减少 NMDAR 介导的电流，和/或荷马和 IP3R 之间的交联减少，这可能会减少细胞内储存的 Ca2+ 的释放。