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<p>Forkhead box protein P2 (Foxp2) regulates the expression of genes related to organ morphogenesis. Homozygous Foxp2(R552H) knock-in (<i>Foxp2</i><sup>R552H/R552H</sup>) mice exhibit abnormal brain development, and die around the weaning period. Here we demonstrate that <i>Foxp2</i><sup>R552H/R552H</sup> mice&#xa0;exhibit abnormal development of gastrointestinal (GI) system, followed by atrophy of stomach, abnormal rotation of intestine, and decreased expression of genes related to GI system development such as <i>bar-like home box 1</i> (<i>BARX1</i>) and <i>secreted frizzled-related protein 1</i> (<i>Sfrp1</i>), antagonist for Wnt/β-catenin signaling,&#xa0;and&#xa0;decreased expression of E-cadherin and Zonula occludens-1 (ZO-1) in epithelium, followed with increase of Zonulin in the serum, marker of leaky gut, and decrease of alpha-smooth muscle actin (SMA) in smooth muscle, resulting in their atrophy. <i>Foxp2</i><sup>+/+</sup> and <i>Foxp2</i><sup>R552H/R552H</sup> transgenic mice expressing <i>Foxp2</i> promoter-mediated mCherry exhibit that <i>Foxp2</i> autoregulates its expression in the developing stomach. Foxp2 may control Wnt/β-catenin signaling via its autoregulation system, but Foxp2(R552H) may not. Our results suggest that <i>Foxp2</i> is necessary for the development of the&#xa0;GI system.</p>

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Abnormal development of gastrointestinal system of homozygous Foxp2(R552H)-mutated mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月17日

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  • Eriko Fujita-Jimbo,
  • Sachie Nakamura,
  • Katsuko Sudo,
  • Takashi Momoi

摘要

Forkhead box protein P2 (Foxp2) regulates the expression of genes related to organ morphogenesis. Homozygous Foxp2(R552H) knock-in (Foxp2R552H/R552H) mice exhibit abnormal brain development, and die around the weaning period. Here we demonstrate that Foxp2R552H/R552H mice exhibit abnormal development of gastrointestinal (GI) system, followed by atrophy of stomach, abnormal rotation of intestine, and decreased expression of genes related to GI system development such as bar-like home box 1 (BARX1) and secreted frizzled-related protein 1 (Sfrp1), antagonist for Wnt/β-catenin signaling, and decreased expression of E-cadherin and Zonula occludens-1 (ZO-1) in epithelium, followed with increase of Zonulin in the serum, marker of leaky gut, and decrease of alpha-smooth muscle actin (SMA) in smooth muscle, resulting in their atrophy. Foxp2+/+ and Foxp2R552H/R552H transgenic mice expressing Foxp2 promoter-mediated mCherry exhibit that Foxp2 autoregulates its expression in the developing stomach. Foxp2 may control Wnt/β-catenin signaling via its autoregulation system, but Foxp2(R552H) may not. Our results suggest that Foxp2 is necessary for the development of the GI system.