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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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Disease models & mechanisms
2026
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41805950/ |
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| author | Kobayashi, Daisuke Urasaki, Akihiro Kimura, Tetsuaki Ansai, Satoshi Matsuo, Kazuhiko Yokoi, Hayato Takashima, Shigeo Kitagawa, Tadao Kage, Takahiro Narita, Takanori Jindo, Tomoko Kinoshita, Masato Naruse, Kiyoshi Nakajima, Yoshiro Shigeta, Masaki Sakaki, Shinichiro Inoue, Satoshi Saba, Rie Yamada, Kei Yokoyama, Takahiko Ishikawa, Yuji Araki, Kazuo Saga, Yumiko Takeda, Hiroyuki Yashiro, Kenta |
| author_facet | Kobayashi, Daisuke Urasaki, Akihiro Kimura, Tetsuaki Ansai, Satoshi Matsuo, Kazuhiko Yokoi, Hayato Takashima, Shigeo Kitagawa, Tadao Kage, Takahiro Narita, Takanori Jindo, Tomoko Kinoshita, Masato Naruse, Kiyoshi Nakajima, Yoshiro Shigeta, Masaki Sakaki, Shinichiro Inoue, Satoshi Saba, Rie Yamada, Kei Yokoyama, Takahiko Ishikawa, Yuji Araki, Kazuo Saga, Yumiko Takeda, Hiroyuki Yashiro, Kenta Kobayashi, Daisuke Urasaki, Akihiro Kimura, Tetsuaki Ansai, Satoshi Matsuo, Kazuhiko Yokoi, Hayato Takashima, Shigeo Kitagawa, Tadao Kage, Takahiro Narita, Takanori Jindo, Tomoko Kinoshita, Masato Naruse, Kiyoshi Nakajima, Yoshiro Shigeta, Masaki Sakaki, Shinichiro Inoue, Satoshi Saba, Rie Yamada, Kei Yokoyama, Takahiko Ishikawa, Yuji Araki, Kazuo Saga, Yumiko Takeda, Hiroyuki Yashiro, Kenta |
| collection | PubMed - marine biology |
| contents | A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation. Kobayashi, Daisuke Urasaki, Akihiro Kimura, Tetsuaki Ansai, Satoshi Matsuo, Kazuhiko Yokoi, Hayato Takashima, Shigeo Kitagawa, Tadao Kage, Takahiro Narita, Takanori Jindo, Tomoko Kinoshita, Masato Naruse, Kiyoshi Nakajima, Yoshiro Shigeta, Masaki Sakaki, Shinichiro Inoue, Satoshi Saba, Rie Yamada, Kei Yokoyama, Takahiko Ishikawa, Yuji Araki, Kazuo Saga, Yumiko Takeda, Hiroyuki Yashiro, Kenta Animals Oryzias Myosin-Light-Chain Phosphatase Disease Models, Animal Intestinal Atresia Intestinal Mucosa Actomyosin Actins Myosin Light Chains Embryo, Nonmammalian Cytoskeleton Phenotype Myosin Heavy Chains Mutation 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. |
| format | Artículo científico |
| id | pubmed_41805950 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Disease models & mechanisms |
| record_format | pubmed |
| spellingShingle | A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation. Kobayashi, Daisuke Urasaki, Akihiro Kimura, Tetsuaki Ansai, Satoshi Matsuo, Kazuhiko Yokoi, Hayato Takashima, Shigeo Kitagawa, Tadao Kage, Takahiro Narita, Takanori Jindo, Tomoko Kinoshita, Masato Naruse, Kiyoshi Nakajima, Yoshiro Shigeta, Masaki Sakaki, Shinichiro Inoue, Satoshi Saba, Rie Yamada, Kei Yokoyama, Takahiko Ishikawa, Yuji Araki, Kazuo Saga, Yumiko Takeda, Hiroyuki Yashiro, Kenta Animals Oryzias Myosin-Light-Chain Phosphatase Disease Models, Animal Intestinal Atresia Intestinal Mucosa Actomyosin Actins Myosin Light Chains Embryo, Nonmammalian Cytoskeleton Phenotype Myosin Heavy Chains Mutation A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation. Kobayashi, Daisuke Urasaki, Akihiro Kimura, Tetsuaki Ansai, Satoshi Matsuo, Kazuhiko Yokoi, Hayato Takashima, Shigeo Kitagawa, Tadao Kage, Takahiro Narita, Takanori Jindo, Tomoko Kinoshita, Masato Naruse, Kiyoshi Nakajima, Yoshiro Shigeta, Masaki Sakaki, Shinichiro Inoue, Satoshi Saba, Rie Yamada, Kei Yokoyama, Takahiko Ishikawa, Yuji Araki, Kazuo Saga, Yumiko Takeda, Hiroyuki Yashiro, Kenta Animals Oryzias Myosin-Light-Chain Phosphatase Disease Models, Animal Intestinal Atresia Intestinal Mucosa Actomyosin Actins Myosin Light Chains Embryo, Nonmammalian Cytoskeleton Phenotype Myosin Heavy Chains Mutation 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. |
| title | A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation. |
| topic | Animals Oryzias Myosin-Light-Chain Phosphatase Disease Models, Animal Intestinal Atresia Intestinal Mucosa Actomyosin Actins Myosin Light Chains Embryo, Nonmammalian Cytoskeleton Phenotype Myosin Heavy Chains Mutation |
| url | https://pubmed.ncbi.nlm.nih.gov/41805950/ |