{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:11:20Z","timestamp":1760145080140,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF) of Korea","award":["2017R1A6A1A03015876","2021R1A6A3A01086488","2021R1A2C1013213","2022R1C1C2004792","2021R1A6C101C369"],"award-info":[{"award-number":["2017R1A6A1A03015876","2021R1A6A3A01086488","2021R1A2C1013213","2022R1C1C2004792","2021R1A6C101C369"]}]},{"name":"Korean government","award":["2017R1A6A1A03015876","2021R1A6A3A01086488","2021R1A2C1013213","2022R1C1C2004792","2021R1A6C101C369"],"award-info":[{"award-number":["2017R1A6A1A03015876","2021R1A6A3A01086488","2021R1A2C1013213","2022R1C1C2004792","2021R1A6C101C369"]}]},{"name":"Korea Basic Science Institute (National Research Facilities and Equipment Center)","award":["2017R1A6A1A03015876","2021R1A6A3A01086488","2021R1A2C1013213","2022R1C1C2004792","2021R1A6C101C369"],"award-info":[{"award-number":["2017R1A6A1A03015876","2021R1A6A3A01086488","2021R1A2C1013213","2022R1C1C2004792","2021R1A6C101C369"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Prion disorders are fatal infectious diseases that are caused by a buildup of pathogenic prion protein (PrPSc) in susceptible mammals. According to new findings, the shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is associated with prion protein (PrP), promoting the progression of prion diseases. Although genetic polymorphisms in SPRN are associated with susceptibility to several prion diseases, genetic polymorphisms in the rabbit SPRN gene have not been investigated in depth. We discovered two novel single nucleotide polymorphisms (SNPs) in the leporine SPRN gene on chromosome 18 and found strong linkage disequilibrium (LD) between them. Additionally, strong LD was not found between the polymorphisms of PRNP and SPRN genes in rabbits. Furthermore, nonsynonymous SNPs that alter the amino acid sequences within the open reading frame (ORF) of SPRN have been observed in prion disease-susceptible animals, but this is the first report in rabbits. As far as we are aware, this study represents the first examination of the genetic features of the rabbit SPRN gene.<\/jats:p>","DOI":"10.3390\/ani14121807","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T08:48:31Z","timestamp":1718614111000},"page":"1807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["First Report of Single Nucleotide Polymorphisms (SNPs) of the Leporine Shadow of Prion Protein Gene (SPRN) and Absence of Nonsynonymous SNPs in the Open Reading Frame (ORF) in Rabbits"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7160-3170","authenticated-orcid":false,"given":"Sameeullah","family":"Memon","sequence":"first","affiliation":[{"name":"Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea"},{"name":"Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zerui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Chan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Andong National University, Andong 36729, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-9994","authenticated-orcid":false,"given":"Byung-Hoon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea"},{"name":"Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Republic of Korea"},{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.5455\/OVJ.2021.v11.i4.23","article-title":"Animal prion diseases: A review of intraspecies transmission","volume":"11","author":"Gallardo","year":"2021","journal-title":"Open Vet. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.molmed.2010.09.001","article-title":"The intricate mechanisms of neurodegeneration in prion diseases","volume":"17","author":"Soto","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/jmg.2008.061804","article-title":"Association of a null allele of SPRN with variant Creutzfeldt-Jakob disease","volume":"45","author":"Beck","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1099\/vir.0.041400-0","article-title":"Association of an indel polymorphism in the 3\u2019UTR of the caprine SPRN gene with scrapie positivity in the central nervous system","volume":"93","author":"Peletto","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s13353-012-0102-4","article-title":"PRNP and SPRN genes polymorphism in atypical bovine spongiform encephalopathy cases diagnosed in Polish cattle","volume":"53","author":"Gurgul","year":"2012","journal-title":"J. Appl. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"942289","DOI":"10.3389\/fvets.2022.942289","article-title":"Novel insertion\/deletion polymorphisms and genetic features of the shadow of prion protein gene (SPRN) in dogs, a prion-resistant animal","volume":"2","author":"Kim","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_7","first-page":"273","article-title":"Shadoo (Sprn) cDNA cloning from sheep adrenals and characterization of full length sheep and mouse SHADC","volume":"22","author":"May","year":"1997","journal-title":"J. Gene Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"31682","DOI":"10.1074\/jbc.M110.118844","article-title":"Unique structural characteristics of the rabbit prion protein","volume":"285","author":"Wen","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1126\/science.182.4107.67","article-title":"Experimental subacute spongiform virus encephalopathies in primates and other laboratory animals","volume":"182","author":"Gibbs","year":"1973","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1128\/JVI.77.3.2003-2009.2003","article-title":"Multiple amino acid residues within the rabbit prion protein inhibit formation of its abnormal isoform","volume":"77","author":"Vorberg","year":"2003","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"27236","DOI":"10.1074\/jbc.M413441200","article-title":"The AGAAAAGA palindrome in PrP is required to generate a productive PrPSc\u2013PrPC complex that leads to prion propagation","volume":"280","author":"Norstrom","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.1038\/sj.emboj.7601830","article-title":"The CNS glycoprotein Shadoo has PrPC-like protective properties and displays reduced levels in prion infections","volume":"26","author":"Watts","year":"2007","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"904305","DOI":"10.3389\/fvets.2022.904305","article-title":"The First Report of Polymorphisms and Genetic Characteristics of the Shadow of Prion Protein (SPRN) in Prion Disease-Resistant Animal, Chickens","volume":"9","author":"Kim","year":"2022","journal-title":"Front. Vet. Sci."},{"doi-asserted-by":"crossref","unstructured":"Kim, Y.C., Kim, H.H., Kim, K., Kim, A.D., and Jeong, B.H. (2022). Novel polymorphisms and genetic characteristics of the shadow of prion protein gene (SPRN) in cats, hosts of feline spongiform encephalopathy. Viruses, 14.","key":"ref_14","DOI":"10.3390\/v14050981"},{"doi-asserted-by":"crossref","unstructured":"Won, S.Y., Kim, Y.C., Do, K., and Jeong, B.H. (2021). The first report of genetic polymorphisms of the equine SPRN gene in outbred horses, jeju and halla horses. Animals, 11.","key":"ref_15","DOI":"10.3390\/ani11092574"},{"doi-asserted-by":"crossref","unstructured":"Won, S.Y., Kim, Y.C., Kim, S.K., and Jeong, B.H. (2019). The First Report of Genetic and Structural Diversities in the SPRN Gene in the Horse, an Animal Resistant to Prion Disease. Genes, 11.","key":"ref_16","DOI":"10.3390\/genes11010039"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15261","DOI":"10.1038\/s41598-019-51625-8","article-title":"Scrapie susceptibility-associated indel polymorphism of shadow of prion protein gene (SPRN) in Korean native black goats","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/85776","article-title":"Variation is the spice of life","volume":"27","author":"Kruglyak","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1229369","DOI":"10.3389\/fvets.2023.1229369","article-title":"First report of a novel polymorphism and genetic characteristics of the leporine prion protein (PRNP) gene","volume":"10","author":"Kim","year":"2023","journal-title":"Front. Vet. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.2741\/3801","article-title":"Biological properties of the PrP-like Shadoo protein","volume":"16","author":"Daude","year":"2011","journal-title":"Front. Biosci. Landmark"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1365-2052.2009.01984.x","article-title":"Identifification of polymorphisms in the ovine Shadow of prion protein (SPRN) gene and assessment of their effect on promoter activity and susceptibility for classical scrapie","volume":"41","author":"Lampo","year":"2010","journal-title":"Anim. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1099\/vir.0.011494-0","article-title":"Genetic analysis of the SPRN gene in ruminants reveals polymorphisms in the alanine-rich segment of shadoo protein","volume":"90","author":"Stewart","year":"2009","journal-title":"J. Gen. Virol."},{"doi-asserted-by":"crossref","unstructured":"Daude, N., Wohlgemuth, S., Rogaeva, E., Farid, A.H., Heaton, M., and Westaway, D. (2009). Frequent missense and insertion\/deletion polymorphisms in the ovine Shadoo gene parallel species-specific variation in PrP. PLoS ONE, 4.","key":"ref_23","DOI":"10.1371\/journal.pone.0006538"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.21775\/cimb.036.067","article-title":"Function of Prion Protein and the Family Member, Shadoo","volume":"36","author":"Onodera","year":"2020","journal-title":"Curr. Issues Mol. Biol."},{"doi-asserted-by":"crossref","unstructured":"Allais-Bonnet, A., and Pailhoux, E. (2014). Role of the prion protein family in the gonads. Front. Cell Dev. Biol., 2.","key":"ref_25","DOI":"10.3389\/fcell.2014.00056"},{"doi-asserted-by":"crossref","unstructured":"Makzhami, S., Passet, B., Halliez, S., Castille, J., Moazami-Goudarzi, K., Duchesne, A., Vilotte, M., Laude, H., Mouillet-Richard, S., and B\u00e9ringue, V. (2014). The prion protein family: A view from the placenta. Front. Cell Dev. Biol., 2.","key":"ref_26","DOI":"10.3389\/fcell.2014.00035"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"123","DOI":"10.5808\/GI.2017.15.4.123","article-title":"Synonymous Codon Usage Controls Various Molecular Aspects","volume":"15","author":"Im","year":"2017","journal-title":"Genom. Inform."},{"doi-asserted-by":"crossref","unstructured":"Won, S.-Y., Kim, Y.-C., Kim, K., Kim, A.-D., and Jeong, B.-H. (2019). The First Report of Polymorphisms and Genetic Features of the prion-like Protein Gene (PRND) in a Prion Disease-Resistant Animal, Dog. Int. J. Mol. Sci., 20.","key":"ref_28","DOI":"10.3390\/ijms20061404"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00335-001-2064-4","article-title":"Genomic organization, comparative analysis, and genetic polymorphisms of the bovine and ovine prion Doppel genes (PRND)","volume":"12","author":"Comincini","year":"2001","journal-title":"Mamm. Genome"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1007\/s003350010285","article-title":"The PrP-like protein Doppel gene in sheep and cattle: cDNA sequence and expression","volume":"12","author":"Tranulis","year":"2001","journal-title":"Mamm. Genome"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1017\/S0022029917000814","article-title":"Bovine spongiform encephalopathy (BSE) associated polymorphisms of the prion-like protein gene (PRND) in Korean dairy cattle and Hanwoo","volume":"85","author":"Kim","year":"2018","journal-title":"J. Dairy Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/age.12004","article-title":"Bovine spongiform encephalopathy (BSE)-associated polymorphisms of the prionprotein (PRNP) gene in Korean native cattle","volume":"44","author":"Jeong","year":"2013","journal-title":"Anim. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1556\/004.2017.028","article-title":"The first report of prion-related protein gene (PRNT) polymorphisms in goat","volume":"65","author":"Kim","year":"2017","journal-title":"Acta Vet. Hung."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/age.12380","article-title":"The prion-related protein (testis-specifc) gene (PRNT) is highly polymorphic in Portuguese sheep","volume":"47","author":"Mesquita","year":"2016","journal-title":"Anim. Genet."},{"doi-asserted-by":"crossref","unstructured":"Jeong, M.J., Kim, Y.C., and Jeong, B.H. (2018). Prion-like protein gene (PRND) polymorphisms associated with scrapie susceptibility in Korean native black goats. PLoS ONE, 13.","key":"ref_35","DOI":"10.1371\/journal.pone.0206209"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/12\/1807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:00:01Z","timestamp":1760108401000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/12\/1807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,17]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ani14121807"],"URL":"https:\/\/doi.org\/10.3390\/ani14121807","relation":{},"ISSN":["2076-2615"],"issn-type":[{"type":"electronic","value":"2076-2615"}],"subject":[],"published":{"date-parts":[[2024,6,17]]}}}