{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:31:49Z","timestamp":1792002709202,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770950, 81470668"],"award-info":[{"award-number":["81770950, 81470668"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Phospholipids are asymmetrically distributed across the mammalian plasma membrane, with phosphatidylserine (<jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content>) and phosphatidylethanolamine concentrated in the cytoplasmic leaflet of the membrane bilayer and phosphatidylcholine in the exoplasmic leaflet. This asymmetric distribution is dependent on a group of P4 <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ases called <jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content> flippases. The proper transport and function of <jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content> flippases require a \u03b2\u2010subunit transmembrane protein 30A (<jats:styled-content style=\"fixed-case\">TMEM<\/jats:styled-content>30A). Disruption of <jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content> flippases leads to several human diseases. <jats:italic>Tmem30a<\/jats:italic> is essential for photoreceptor survival. However, the roles of <jats:italic>Tmem30a<\/jats:italic> in the retinal rod bipolar cells (<jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>) remain elusive. To investigate the role of <jats:italic>Tmem30a<\/jats:italic> in the <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>s, we generated a <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>\u2010specific <jats:italic>Tmem30a<\/jats:italic> knockout (<jats:styled-content style=\"fixed-case\">cKO<\/jats:styled-content>) mouse model using <jats:styled-content style=\"fixed-case\">PCP<\/jats:styled-content>2\u2010Cre line. The <jats:italic>Tmem30a <\/jats:italic><jats:styled-content style=\"fixed-case\">cKO<\/jats:styled-content> mice exhibited defect in <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> function and progressive <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> death. <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\u03b1 staining of retinal cryosections from <jats:styled-content style=\"fixed-case\">cKO<\/jats:styled-content> mice revealed a remarkable dendritic sprouting of rod bipolar cells during the early degenerative process. Immunostaining analysis of <jats:styled-content style=\"fixed-case\">PSD<\/jats:styled-content>95 and <jats:styled-content style=\"fixed-case\">mG<\/jats:styled-content>luT6 expression demonstrated that rod bipolar cells in <jats:italic>Tmem30a <\/jats:italic><jats:styled-content style=\"fixed-case\">cKO<\/jats:styled-content> retinas exhibited aberrant dendritic sprouting as a result of impaired synaptic efficacy, which implied a crucial role for <jats:italic>Tmem30a<\/jats:italic> in synaptic transmission in the retina. In addition, loss of <jats:italic>Tmem30a<\/jats:italic> led to reactive gliosis with increased expression of glial fibrillary acidic protein and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>68. <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> staining suggested that apoptotic cell death occurred in the retinal inner nuclear layer (<jats:styled-content style=\"fixed-case\">INL<\/jats:styled-content>). Our data show that loss of <jats:italic>Tmem30a<\/jats:italic> in <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content>s results in dendritic sprouting of rod bipolar cells, increased astrogliosis and <jats:styled-content style=\"fixed-case\">RBC<\/jats:styled-content> death. Taken together, our studies demonstrate an essential role for <jats:italic>Tmem30a<\/jats:italic> in the retinal bipolar cells.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14643-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Cover Image for this issue: doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1111\/jnc.14492\">10.1111\/jnc.14492<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14643","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T17:54:49Z","timestamp":1544637289000},"page":"400-412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["<i>Tmem30a<\/i> deficiency leads to retinal rod bipolar cell degeneration"],"prefix":"10.1111","volume":"148","author":[{"given":"Yeming","family":"Yang","sequence":"first","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Provincial Key Laboratory for Human Disease Gene Study Sichuan Provincial 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