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To model BSCL2 disease, we generated an orthologous BSCL2 variant, seip-1(A185P), in Caenorhabditis elegans. In this study, we conducted an unbiased chemical mutagenesis screen to identify genetic suppressors that restore embryonic viability in the seip-1(A185P) mutant background. A total of five suppressor lines were isolated and recovered from the screen. The defective phenotypes of seip-1(A185P), including embryonic lethality and impaired eggshell formation, were significantly suppressed in each suppressor line. Two of the five suppressor lines also alleviated the enlarged LDs in the oocytes. We then mapped a suppressor candidate gene, lmbr-1, which is an ortholog of human limb development membrane protein 1 (LMBR1). The CRISPR\/Cas9 edited lmbr-1 suppressor alleles, lmbr-1(S647F) and lmbr-1(P314L), both significantly suppressed embryonic lethality and defective eggshell formation in the seip-1(A185P) background. The newly identified suppressor lines offer valuable insights into potential genetic interactors and pathways that may regulate seipin in the lipodystrophy model.<\/jats:p>","DOI":"10.1242\/dmm.050524","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T03:42:08Z","timestamp":1709869328000},"source":"Crossref","is-referenced-by-count":3,"title":["Identification of genetic suppressors for a BSCL2 lipodystrophy pathogenic variant in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8179-8162","authenticated-orcid":false,"given":"Xiaofei","family":"Bai","sequence":"first","affiliation":[{"name":"University of Florida 1 Department of Biology , , Gainesville, FL 32610 , USA"},{"name":"Genetics Institute, University of Florida 2 , Gainesville, FL 32610 , USA"},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 3 , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3517-5973","authenticated-orcid":false,"given":"Harold E.","family":"Smith","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 3 , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-2031","authenticated-orcid":false,"given":"Andy","family":"Golden","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 3 , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"2024072207204182500_DMM050524C1","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.molmed.2004.07.009","article-title":"Seipin: a mysterious protein","volume":"10","author":"Agarwal","year":"2004","journal-title":"Trends Mol. 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