{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:36:58Z","timestamp":1772001418885,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP20K21655"],"award-info":[{"award-number":["JP20K21655"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP20K08885"],"award-info":[{"award-number":["JP20K08885"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP23K05850"],"award-info":[{"award-number":["JP23K05850"]}]},{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP24K09998"],"award-info":[{"award-number":["JP24K09998"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JDB"],"abstract":"<jats:p>The mouse Harderian gland (HG) is a secretory gland that covers the posterior portion of the eyeball, opening at the base of the nictitating membrane. The HG serves to protect the eye surface from infection with its secretions. Mice open their eyelids at about 2 weeks of age, and the development of the HG primordium mechanically opens the eye by pushing the eyeball from its rear. Therefore, when HG formation is disturbed, the eye exhibits enophthalmos (the slit-eye phenotype), and a line of Fgf10+\/\u2212 heterozygous loss-of-function mice exhibits slit-eye due to the HG atrophy. However, it has not been clarified how and when HGs degenerate and atrophy in Fgf10+\/\u2212 mice. In this study, we observed the HGs in embryonic (E13.5 to E19), postnatal (P0.5 to P18) and 74-week-old Fgf10+\/\u2212 mice. We found that more than half of the Fgf10+\/\u2212 mice had markedly degenerated HGs, often unilaterally. The degenerated HG tissue had a melanized appearance and was replaced by connective tissue, which was observed by P10. The development of HGs was delayed or disrupted in the similar proportion of Fgf10+\/\u2212 embryos, as revealed via histology and the loss of HG-marker expression. In situ hybridization showed Fgf10 expression was observed in the Harderian mesenchyme in wild-type as well as in the HG-lacking heterozygote at E19. These results show that the Fgf10 haploinsufficiency causes delayed or defective HG development, often unilaterally from the unexpectedly early neonatal period.<\/jats:p>","DOI":"10.3390\/jdb12020016","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T08:19:42Z","timestamp":1717402782000},"page":"16","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Harderian Gland Development and Degeneration in the Fgf10-Deficient Heterozygous Mouse"],"prefix":"10.3390","volume":"12","author":[{"given":"Shiori","family":"Ikeda","sequence":"first","affiliation":[{"name":"Department of Cytology and Histology, Medical School, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7089-2951","authenticated-orcid":false,"given":"Keita","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2993-4635","authenticated-orcid":false,"given":"Hitomi","family":"Ono-Minagi","sequence":"additional","affiliation":[{"name":"Department of Cytology and Histology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Miyaishi","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0351-5603","authenticated-orcid":false,"given":"Tsutomu","family":"Nohno","sequence":"additional","affiliation":[{"name":"Department of Cytology and Histology, Medical School, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-606X","authenticated-orcid":false,"given":"Hideyo","family":"Ohuchi","sequence":"additional","affiliation":[{"name":"Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.aanat.2006.01.018","article-title":"The primate Harderian gland: Does it really exist?","volume":"188","author":"Rehorek","year":"2006","journal-title":"Ann. 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