Scholarlink

<p>Mutations in the chromatin-remodelling factor ATRX cause syndromic intellectual disability (ID) and autism spectrum disorder (ASD), but the role of microglial ATRX in early brain development remains poorly understood. Here, we used a tamoxifen-inducible Cx3cr1-CreERT2 system to delete <i>Atrx</i> specifically in microglia during the first postnatal week. High recombination efficiency was achieved by one month of age; however, knockout efficiency declined by three months to approximately 20% in the cortex and 40% in the hippocampus, suggesting repopulation by wild-type microglia. ATRX<b>-</b>deficient microglia exhibit an increase in CD68-positive foci, greater ramification complexity, and enlarged cell volume, consistent with a reactive phenotype. Furthermore, we observed an elevated proportion of Ki67-positive proliferative microglia at both one and three months of age. To assess the functional consequences of these cellular alterations, we evaluated juvenile and adult ATRX microglial knockout (mi-KO) and control mice across a behavioural battery assessing anxiety-like behaviour, locomotion, learning and memory, social interaction, and sensory gating. No significant genotype-dependent differences were detected across these domains. Together, these findings indicate that perinatal loss of ATRX in microglia induces a reactive phenotype and turnover without measurable impacts on neurobehavioural outcomes, suggesting developmental resilience of neural circuits to transient microglial dysregulation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Spared cognitive and social function following perinatal ablation of ATRX despite transient microglia dysregulation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月9日

查看全文
  • Kasha Y. Mansour,
  • Miguel A. Pena-Ortiz,
  • Jasper Wu,
  • Sarfraz Shafiq,
  • Nathalie G. Bérubé

摘要

Mutations in the chromatin-remodelling factor ATRX cause syndromic intellectual disability (ID) and autism spectrum disorder (ASD), but the role of microglial ATRX in early brain development remains poorly understood. Here, we used a tamoxifen-inducible Cx3cr1-CreERT2 system to delete Atrx specifically in microglia during the first postnatal week. High recombination efficiency was achieved by one month of age; however, knockout efficiency declined by three months to approximately 20% in the cortex and 40% in the hippocampus, suggesting repopulation by wild-type microglia. ATRX-deficient microglia exhibit an increase in CD68-positive foci, greater ramification complexity, and enlarged cell volume, consistent with a reactive phenotype. Furthermore, we observed an elevated proportion of Ki67-positive proliferative microglia at both one and three months of age. To assess the functional consequences of these cellular alterations, we evaluated juvenile and adult ATRX microglial knockout (mi-KO) and control mice across a behavioural battery assessing anxiety-like behaviour, locomotion, learning and memory, social interaction, and sensory gating. No significant genotype-dependent differences were detected across these domains. Together, these findings indicate that perinatal loss of ATRX in microglia induces a reactive phenotype and turnover without measurable impacts on neurobehavioural outcomes, suggesting developmental resilience of neural circuits to transient microglial dysregulation.