{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T13:27:06Z","timestamp":1793626026152,"version":"4.5.1"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP256f0137008"],"award-info":[{"award-number":["JP256f0137008"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Systemic metabolism critically depends on thyroid hormones, whose release relies heavily on proper lysosomal function for thyroglobulin degradation. MROH1, a highly conserved mediator of lysosomal membrane fission, is predominantly expressed in the human thyroid gland; however, its physiological role within endocrine systems remains unexplored. This study investigated the impact of MROH1 deficiency on thyroid function using a novel global\n                      <jats:italic>Mroh1<\/jats:italic>\n                      knockout (KO) mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Metabolic phenotypes, including body weight and serum biochemical parameters (FT3, FT4, TSH, and cholesterol), were evaluated in male\n                      <jats:italic>Mroh1<\/jats:italic>\n                      \u2010KO mice and their controls. Thyroid architecture and gene expression profiles were investigated via histological analysis and quantitative reverse transcription\u2010PCR (qRT\u2010PCR). Lysosomal function was assessed using immunoblotting and cathepsin L proteolytic activity assays in primary thyroid cells and whole\u2010tissue lysates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Mroh1<\/jats:italic>\n                      \u2010KO mice showed reduced circulating thyroid hormone levels characterized by significantly reduced serum FT4 and FT3 levels, a gradual increase in body weight, and hypercholesterolemia. Histological analysis of aged\n                      <jats:italic>Mroh1<\/jats:italic>\n                      \u2010KO mice revealed an altered thyroid architecture, featuring smaller follicle sizes and the replacement of follicles with adipocyte\u2010like structures. Although lysosomal biogenesis and cathepsin L protease activities remained preserved, the expression of key thyroid differentiation regulators (\n                      <jats:italic>Nkx2\u20101<\/jats:italic>\n                      ,\n                      <jats:italic>Foxe1<\/jats:italic>\n                      ) and their downstream targets (\n                      <jats:italic>Tg<\/jats:italic>\n                      ,\n                      <jats:italic>Mct8<\/jats:italic>\n                      ) were significantly downregulated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Global\n                      <jats:italic>Mroh1<\/jats:italic>\n                      deficiency is associated with reduced circulating thyroid hormone levels, thyroid architectural remodelling, and downregulated thyroid\u2010specific gene expression. These findings demonstrate that MROH1 is important for maintaining thyroid gland hormone homeostasis and structural integrity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70348","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:16:54Z","timestamp":1789730214000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>HEAT<\/scp>\n                    Repeat Protein\n                    <scp>MROH1<\/scp>\n                    Deficiency Leads to Reduced Circulating Thyroid Hormone Levels in Mice"],"prefix":"10.1002","volume":"9","author":[{"given":"Nami","family":"Ohuchi","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1425-7790","authenticated-orcid":false,"given":"Yoshinori","family":"Osaki","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8710-5232","authenticated-orcid":false,"given":"Yoshimi","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Araki","sequence":"additional","affiliation":[{"name":"Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6716-1544","authenticated-orcid":false,"given":"Yuhei","family":"Mizunoe","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology &amp; Metabolic Disease, Faculty of Pharmaceutical Sciences Tokyo University of Science  Noda Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8780-8536","authenticated-orcid":false,"given":"Takaaki","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-3616","authenticated-orcid":false,"given":"Yuki","family":"Murayama","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0508-3266","authenticated-orcid":false,"given":"Yoko","family":"Sugano","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8081-6226","authenticated-orcid":false,"given":"Hitoshi","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5898-3463","authenticated-orcid":false,"given":"Takashi","family":"Matsuzaka","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5170-9699","authenticated-orcid":false,"given":"Motohiro","family":"Sekiya","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-5572","authenticated-orcid":false,"given":"Hitoshi","family":"Shimano","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Institute of Medicine, University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"StatPearls [Internet]","author":"Khan Y. 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