{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:43:07Z","timestamp":1792395787861,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and serious congenital disorder with poor outcomes, where a heterozygous missense mutation is present in the\n                      <jats:italic>ACTG2<\/jats:italic>\n                      gene. Here, we aimed to investigate the pathogenesis of\n                      <jats:italic>ACTG2<\/jats:italic>\n                      in MMIHS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cohort with 20 patients with MMIHS was screened.\n                      <jats:italic>Actg2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>R257C<\/jats:italic>\n                      <\/jats:sup>\n                      heterozygous mutant mice were generated using the CRISPR\/Cas9 system. Gastrointestinal (GI) motility, voluntary urination, collagen gel contraction, and G\u2010actin\/F\u2010actin analysis were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      The R257C variant of\n                      <jats:italic>ACTG2<\/jats:italic>\n                      most frequently occurred in patients with MMIHS and demonstrated the typical symptoms of MMIHS.\n                      <jats:italic>Actg2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>R257C<\/jats:italic>\n                      <\/jats:sup>\n                      heterozygous mutant mice had dilated intestines and bladders. The functional assay showed a prolonged total time of GI transit and decreased urine spot area. Collagen gel contraction assay and G\u2010actin\/F\u2010actin analysis indicated that mutant mice showed reduced area of contraction of smooth muscle cells (SMCs) and impaired actin polymerization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions &amp; Inferences<\/jats:title>\n                    <jats:p>\n                      A mouse model demonstrating MMIHS\u2010like symptoms was generated. The\n                      <jats:italic>Actg2<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>R257C<\/jats:italic>\n                      <\/jats:sup>\n                      heterozygous variant impairs SMCs contraction by interfering with actin polymerization, leading to GI motility disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.14472","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T09:37:54Z","timestamp":1666258674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Heterozygous\n                    <scp>\n                      <i>Actg2<\/i>\n                      <sup>\n                        <i>R257C<\/i>\n                      <\/sup>\n                    <\/scp>\n                    mice mimic the phenotype of megacystis microcolon intestinal hypoperistalsis syndrome"],"prefix":"10.1111","volume":"35","author":[{"given":"Hui","family":"Cai","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition  Shanghai China"},{"name":"Shanghai Institute of Pediatric Research  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Pediatric 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