{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:04:00Z","timestamp":1790687040623,"version":"4.1.0"},"reference-count":18,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":1964,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"name":"International Science and Technology Cooperation Program of China","award":["2013DFG32700"],"award-info":[{"award-number":["2013DFG32700"]}]},{"name":"Key Research Program of Shandong Province","award":["2015GSF118141"],"award-info":[{"award-number":["2015GSF118141"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2015HZ002 ZR2016HQ19"],"award-info":[{"award-number":["ZR2015HZ002 ZR2016HQ19"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The S113R mutation (c.339T&amp;gt;G) (MIM #603690.0001) in SLC33A1 (MIM #603690), an ER membrane acetyl-CoA transporter, has been previously identified in patients with hereditary spastic paraplegia type 42 (SPG42; MIM #612539). SLC33A1 has also been shown to inhibit bone morphogenetic protein (BMP) signaling pathway in zebrafish. To better understand the function of SLC33A1, we generated and characterized Slc33a1S113R knock-in mice. Homozygous Slc33a1S113R mutant mice were embryonic lethal, while heterozygous Slc33a1 mutant mice (Slc33a1wt\/mut) exhibited behavioral abnormalities and central neurodegeneration, which is consistent with HSP phenotypes. Importantly, we found an upregulation of BMP signaling in the nervous system and mouse embryonic fibroblasts of Slc33a1wt\/mut mice. Using a sciatic nerve crush injury model in vivo and dorsal root ganglion (DRG) culture in vitro we showed that injury-induced axonal regeneration in Slc33a1wt\/mut mice was accelerated and was mediated by upregulated BMP signaling. Exogenous addition of BMP signaling antagonist, Noggin, could efficiently alleviate the accelerated injury-induced axonal regrowth. These results indicate that SLC33A1 can negatively regulate BMP signaling in mice, further supporting the notion that upregulation of BMP signaling is a common mechanism of a subset of hereditary spastic paraplegias.<\/jats:p>","DOI":"10.1242\/dmm.026880","type":"journal-article","created":{"date-parts":[[2016,11,25]],"date-time":"2016-11-25T01:35:19Z","timestamp":1480037719000},"source":"Crossref","is-referenced-by-count":15,"title":["S113R mutation in Slc33a1 leads to neurodegeneration and augmented BMP signaling in a mouse model"],"prefix":"10.1242","author":[{"given":"Pingting","family":"Liu","sequence":"first","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baichun","family":"Jiang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ma","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinshuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changshun","family":"Shao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-1712","authenticated-orcid":false,"given":"Wenjie","family":"Sun","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoqin","family":"Gong","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, Shandong University School of Medicine, Jinan, Shandong 250012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2016,1,1]]},"reference":[{"key":"2021042701332621700_DMM026880C1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1146\/annurev-neuro-062111-150400","article-title":"Cellular pathways of hereditary spastic paraplegia","volume":"35","author":"Blackstone","year":"2012","journal-title":"Annu. 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