{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:41:00Z","timestamp":1759945260401,"version":"build-2065373602"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H00445","21H00227","22K06022"],"award-info":[{"award-number":["20H00445","21H00227","22K06022"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cerebellar, ocular, craniofacial, and genital (COFG) syndrome is a human genetic disease that is caused by <jats:italic>MAB21L1<\/jats:italic> mutations. A COFG mouse model with <jats:italic>Mab21l1<\/jats:italic>\u2010null mutation causes severe microphthalmia and fontanelle dysosteogenesis, similar to the symptoms in human patients. One of the typical symptoms is scrotal agenesis in male infants, while male <jats:italic>Mab21l1<\/jats:italic>\u2010null mice show hypoplastic preputial glands, a rodent\u2010specific derivative of the cranial scrotal fold. However, it is still unclear where and how MAB21Ll acts in the external genitalia in both mice and humans. Here we show that, at the neonatal stage, MAB21L1 expression in the external genitalia was restricted to two mesenchymal cell populations\u2014underneath the scrotal and labial skin and around the preputial and clitoral glands (PG\/CG). Morphometric analyses of the <jats:italic>Mab21l1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> pups revealed a significant reduction in the external size of the scrotum, vulva, and CG, as well as PG. In the periglandular region around PG and CG, the periglandular mesenchymal cells showed a drastic reduction in both cell density and immunoreactive signals for several extracellular matrix proteins (e.g., collagen I, fibronectin, and proteoglycans), together with their reduced Ki67\u2010positive cell proliferation index. In the <jats:italic>Mab21l1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> PG\/CG, together with reduced vascularization, the glandular epithelia displayed atrophy with discontinuous basal lamina along the basal surface and defective glycogen accumulation in their cytoplasm. Under a 5\u2010day organ culture of the isolated PG, the <jats:italic>Mab21l1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> explants showed poor outgrowth and retention of the glandular structure in vitro. However, the addition of exogenous Matrigel could partially rescue such tissue\u2010autonomous phenotypes, showing glandular morphology similar to that of the wild\u2010type explants. These findings suggest that MAB21L1+ mesenchymal cells play a crucial role in providing nutrient ECM support for glandular outgrowth and morphogenesis in the peripheral external genitalia.<\/jats:p>","DOI":"10.1002\/ar.25330","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T05:55:05Z","timestamp":1695707705000},"page":"1943-1959","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["External genitalia phenotypes of a <i>Mab21l1<\/i>\u2010null mouse model for cerebellar, ocular, craniofacial, and genital (COFG) syndrome"],"prefix":"10.1002","volume":"307","author":[{"given":"Watcharapon","family":"Promsut","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuichi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy The University of Tokyo  Tokyo Japan"},{"name":"Department of Applied Biological Chemistry The University of Tokyo  Tokyo Japan"},{"name":"RNA Company Limited  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Takami","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanae","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mami","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry The University of Tokyo  Tokyo Japan"},{"name":"RNA Company Limited  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-7806","authenticated-orcid":false,"given":"Yoshiakira","family":"Kanai","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0362-x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.2.515"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1066896906291779"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12794"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.11.3615"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.572511"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091810104"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep27498"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.12433"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.117903"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.1161"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00705-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp854"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90242-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00455"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.13.2397"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.09.004"},{"key":"e_1_2_7_20_1","first-page":"1","article-title":"Single amino acid variation in MAB21L1 is dominantly associated with congenital eye defects","volume":"0","author":"Meng F.","year":"2022","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2017.11.001"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0668"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105623"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.14232\/abs.2020.2.181-189"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032991"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20135348"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.312"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.560"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24218"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.03.017"},{"volume-title":"Gray's anatomy e\u2010book: The anatomical basis of clinical practice","year":"2021","author":"Standring S.","key":"e_1_2_7_31_1"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.21279"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.10018"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00012-6"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204203"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00399"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.07.016"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049251"},{"issue":"5","key":"e_1_2_7_39_1","first-page":"370","article-title":"Endothelial degeneration of Parkinson disease is related to alpha\u2010synuclein aggregation","volume":"7","author":"Yang P.","year":"2017","journal-title":"Journal of Alzheimers Disease & Parkinsonism"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24923"}],"container-title":["The Anatomical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.25330","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:58:37Z","timestamp":1759942717000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/ar.25330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/ar.25330"],"URL":"https:\/\/doi.org\/10.1002\/ar.25330","archive":["Portico"],"relation":{},"ISSN":["1932-8486","1932-8494"],"issn-type":[{"type":"print","value":"1932-8486"},{"type":"electronic","value":"1932-8494"}],"subject":[],"published":{"date-parts":[[2023,9,26]]},"assertion":[{"value":"2023-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}