Scholarlink

<p>Single allelic mutations in the <i>FOXG1</i> gene lead to FOXG1 syndrome (FS). To understand the pathophysiology of FS, which vary depending on FOXG1 mutation types, patient-specific animal models are critical. Here, we report a patient-specific <i>Q84Pfs</i> heterozygous (Q84Pfs-Het) mouse model, which recapitulates various FS phenotypes across cellular, brain structural, and behavioral levels. Q84Pfs-Het cortex shows dysregulations of genes controlling cell proliferation, neuronal projection and migration, synaptic assembly, and synaptic vesicle transport. The <i>Q84Pfs</i> allele produces the N-terminal fragment of FOXG1 (Q84Pfs protein) in Q84Pfs-Het mouse brains, which forms intracellular speckles, interacts with FOXG1 full-length protein, and triggers the sequestration of FOXG1 to distinct subcellular domains. Q84Pfs protein promotes the radial glial cell identity and suppresses neuronal migration in the cortex. Our study uncovers the role of the FOXG1 fragment from FS-causing <i>FOXG1</i> variants and identifies the genes involved in FS-like cellular and behavioral phenotypes, providing insights into the pathophysiology of FS.</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

The patient-specific mouse model with Foxg1 frameshift mutation provides insights into the pathophysiology of FOXG1 syndrome

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月22日

查看全文
  • Shin Jeon,
  • Jaein Park,
  • Ji Hwan Moon,
  • Dongjun Shin,
  • Liwen Li,
  • Holly O’Shea,
  • Seon-Ung Hwang,
  • Hyo-Jong Lee,
  • Elise Brimble,
  • Jae W. Lee,
  • Stewart D. Clark,
  • Soo-Kyung Lee

摘要

Single allelic mutations in the FOXG1 gene lead to FOXG1 syndrome (FS). To understand the pathophysiology of FS, which vary depending on FOXG1 mutation types, patient-specific animal models are critical. Here, we report a patient-specific Q84Pfs heterozygous (Q84Pfs-Het) mouse model, which recapitulates various FS phenotypes across cellular, brain structural, and behavioral levels. Q84Pfs-Het cortex shows dysregulations of genes controlling cell proliferation, neuronal projection and migration, synaptic assembly, and synaptic vesicle transport. The Q84Pfs allele produces the N-terminal fragment of FOXG1 (Q84Pfs protein) in Q84Pfs-Het mouse brains, which forms intracellular speckles, interacts with FOXG1 full-length protein, and triggers the sequestration of FOXG1 to distinct subcellular domains. Q84Pfs protein promotes the radial glial cell identity and suppresses neuronal migration in the cortex. Our study uncovers the role of the FOXG1 fragment from FS-causing FOXG1 variants and identifies the genes involved in FS-like cellular and behavioral phenotypes, providing insights into the pathophysiology of FS.