論文 - 詳細
| RRC ID | 87810 |
|---|---|
| 著者 | Kobayashi D, Urasaki A, Kimura T, Ansai S, Matsuo K, Yokoi H, Takashima S, Kitagawa T, Kage T, Narita T, Jindo T, Kinoshita M, Naruse K, Nakajima Y, Shigeta M, Sakaki S, Inoue S, Saba R, Yamada K, Yokoyama T, Ishikawa Y, Araki K, Saga Y, Takeda H, Yashiro K. |
| タイトル | A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation. |
| ジャーナル | Dis Model Mech |
| Abstract |
Congenital intestinal atresia (IA) is a birth defect characterised by the absence or closure of part of the intestine. Although genetic factors are implicated, mechanistic understanding has been hindered by the lack of suitable animal models. Here, we describe a medaka (Oryzias latipes) mutant, generated by N-ethyl-N-nitrosourea (ENU) mutagenesis, that develops IA during embryogenesis. Positional cloning identified a nonsense mutation in mypt1, encoding myosin phosphatase target subunit 1. Mutant embryos exhibited ectopic accumulation of F-actin and phosphorylated myosin regulatory light chain (Mrlc) in the intestinal epithelium, consistent with disrupted actomyosin regulation. These cytoskeletal abnormalities were accompanied by epithelial disorganisation, without notable alterations in cell proliferation, motility or apoptosis. Inhibition of myh11a, encoding smooth muscle (SM) myosin heavy chain, ameliorated the IA phenotype, whereas blebbistatin treatment completely rescued the defect, suggesting a non-contractile role prior to SM maturation. Together, these findings demonstrate that mypt1 loss disrupts intestinal morphogenesis through actomyosin dysregulation. Given the recent clinical identification of IA associated with MYPT1 variants, this medaka model offers a valuable platform to investigate the developmental and molecular basis of MYPT1-associated IA in humans. |
| 巻・号 | 19(2) |
| 公開日 | 2026-2-1 |
| DOI | 10.1242/dmm.052605 |
| PII | 370912 |
| PMID | 41805950 |
| PMC | PMC13035062 |
| MeSH | Actins / metabolism Actomyosin / metabolism Animals Codon, Nonsense / genetics Cytoskeleton / drug effects Cytoskeleton / metabolism Disease Models, Animal Embryo, Nonmammalian / drug effects Embryo, Nonmammalian / metabolism Embryo, Nonmammalian / pathology Ethylnitrosourea Fish Proteins* / genetics Fish Proteins* / metabolism Intestinal Atresia* / embryology Intestinal Atresia* / genetics Intestinal Atresia* / pathology Intestinal Mucosa* / metabolism Intestinal Mucosa* / pathology Models, Genetic* Mutagenesis Myosin Heavy Chains / metabolism Myosin Light Chains / metabolism Myosin-Light-Chain Phosphatase* / genetics Myosin-Light-Chain Phosphatase* / metabolism Oryzias* / embryology Oryzias* / genetics Phenotype Phosphorylation |
| IF | 4.651 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 1.5 |
| リソース情報 | |
| メダカ | MT147 |