{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T08:14:11Z","timestamp":1780733651955,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>To elucidate the functional role of V-set and immunoglobulin domain-containing 1 (VSIG1) in spermatogenesis and fertilization, we knocked out (KO) VSIG1 in a mouse embryo using CRISPR\/Cas9 (Clustered regularly interspaced short palindromic repeat\/CRISPR-associated protein 9) -mediated genome editing. Reverse transcription PCR was performed using cDNA synthesized from VSIG1 KO testis RNA. Although Western blot analysis using a specific antibody to VSIG1 confirmed VSIG1 protein defects in the KO mice, hematoxylin-eosin staining analysis was similar in the KO and wild-type mice. Additionally, computer-assisted sperm analysis and in vitro fertilization experiments were conducted to confirm the activity and fertilization ability of sperm derived from the KO mouse. Mice lacking VSIG1 were viable and had no serious developmental defects. As they got older, the KO mice showed slightly higher weight loss, male mice lacking VSIG1 had functional testes, including normal sperm number and motility, and both male and female mice lacking VSIG1 were fertile. Our results from VSIG1 KO mice suggest that VSIG1 may not play essential roles in spermatogenesis and normal testis development, function, and maintenance. VSIG1 in sperm is dispensable for spermatogenesis and male fertility in mice. As several genes are known to possess slightly different functions depending on the species, the importance and molecular mechanism of VSIG1 in tissues of other species needs further investigation.<\/jats:p>","DOI":"10.3390\/ani11041037","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T03:52:03Z","timestamp":1617767523000},"page":"1037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["V-Set and Immunoglobulin Domain-Containing 1 (VSIG1), Predominantly Expressed in Testicular Germ Cells, Is Dispensable for Spermatogenesis and Male Fertility in Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Yena","family":"Jung","sequence":"first","affiliation":[{"name":"College of Pharmacy, Catholic University of Daegu, Gyeongsan-si 38430, Korea"},{"name":"Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Bang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Catholic University of Daegu, Gyeongsan-si 38430, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Catholic University of Daegu, Gyeongsan-si 38430, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaeli","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Catholic University of Daegu, Gyeongsan-si 38430, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Rae","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, School of Medicine, Ajou University, Yeongtong-gu, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2649-9677","authenticated-orcid":false,"given":"Jeong-Woong","family":"Lee","sequence":"additional","affiliation":[{"name":"Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB),  Deajeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0489-6719","authenticated-orcid":false,"given":"Bong-Seok","family":"Song","sequence":"additional","affiliation":[{"name":"Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4492-1085","authenticated-orcid":false,"given":"Bo-Woong","family":"Sim","sequence":"additional","affiliation":[{"name":"Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Won","family":"Seol","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabbine","family":"Wee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Environmental Horticulture, University of Seoul, Seoul 02504, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Uk","family":"Kim","sequence":"additional","affiliation":[{"name":"Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekyune","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Catholic University of Daegu, Gyeongsan-si 38430, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"ref_1","unstructured":"Knobii, E., and Neill, J.D. (1994). The Physiology of Reproduction, Raven Press. [2nd ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1095\/biolreprod56.2.320","article-title":"Why did the sperm cross the cumulus? To get to the oocyte. Functions of the sperm surface proteins PH-20 and fertilin in arriving at, and fusing with, the egg","volume":"56","author":"Myles","year":"1997","journal-title":"Biol. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0945-053X(01)00171-8","article-title":"The dual functions of GPI-anchored PH-20: Hyaluronidase and intracellular signaling","volume":"20","author":"Cherr","year":"2001","journal-title":"Matrix Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1126\/science.1072029","article-title":"Penetration, adhesion, and fusion in mammalian sperm-egg interaction","volume":"296","author":"Primakoff","year":"2002","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.fertnstert.2013.01.111","article-title":"The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility","volume":"99","author":"Kovac","year":"2013","journal-title":"Fertil Steril"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"350","DOI":"10.4103\/1008-682X.178857","article-title":"Recent advances in the genetics of testicular failure","volume":"18","author":"Song","year":"2016","journal-title":"Asian J. Androl"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1469-1809.1975.tb00126.x","article-title":"Cytogenetics and infertility in man. I. Karyotype and seminal analysis: Results of a five-year survey of men attending a subfertility clinic","volume":"39","author":"Chandley","year":"1975","journal-title":"Ann. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ke, C.C., Lin, Y.H., Wang, Y.Y., Wu, Y.Y., Chen, M.F., Ku, W.C., Chiang, H.S., and Lai, T.H. (2018). TBC1D21 Potentially Interacts with and Regulates Rap1 during Murine Spermatogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113292"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1210\/er.2003-0022","article-title":"Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis","volume":"25","author":"Mruk","year":"2004","journal-title":"Endocr. Rev."},{"key":"ref_10","first-page":"2","article-title":"Glycoprotein A34, a novel target for antibody-based cancer immunotherapy","volume":"6","author":"Scanlan","year":"2006","journal-title":"Cancer Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s10059-010-0138-4","article-title":"Extracellular domain of V-set and immunoglobulin domain containing 1 (VSIG1) interacts with sertoli cell membrane protein, while its PDZ-binding motif forms a complex with ZO-1","volume":"30","author":"Kim","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Oidovsambuu, O., Nyamsuren, G., Liu, S., Goring, W., Engel, W., and Adham, I.M. (2011). Adhesion protein VSIG1 is required for the proper differentiation of glandular gastric epithelia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025908"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/jso.22150","article-title":"Decreased expression of V-set and immunoglobulin domain containing 1 (VSIG1) is associated with poor prognosis in primary gastric cancer","volume":"106","author":"Chen","year":"2012","journal-title":"J. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.18632\/oncotarget.13683","article-title":"Immunoglobulin superfamily genes are novel prognostic biomarkers for breast cancer","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00005-012-0199-5","article-title":"Function of junctional adhesion molecules (JAMs) in leukocyte migration and homeostasis","volume":"61","author":"Arcangeli","year":"2013","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.addr.2005.01.005","article-title":"The JAM family of proteins","volume":"57","author":"Mandell","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"354","DOI":"10.33594\/000000224","article-title":"CRISPR\/Cas9 Technology in Translational Biomedicine","volume":"54","author":"Leonova","year":"2020","journal-title":"Cell Physiol. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/B978-0-12-801185-0.00015-5","article-title":"CRISPR\/Cas9-based genome editing in mice by single plasmid injection","volume":"546","author":"Fujihara","year":"2014","journal-title":"Methods Enzymol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00335-014-9524-0","article-title":"Simple generation of albino C57BL\/6J mice with G291T mutation in the tyrosinase gene by the CRISPR\/Cas9 system","volume":"25","author":"Mizuno","year":"2014","journal-title":"Mamm. Genome"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1038\/s41598-019-39950-4","article-title":"A simple genotyping method to detect small CRISPR-Cas9 induced indels by agarose gel electrophoresis","volume":"9","author":"Bhattacharya","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0006-291X(03)00588-6","article-title":"Differential localization of ADAM1a and ADAM1b in the endoplasmic reticulum of testicular germ cells and on the surface of epididymal sperm","volume":"304","author":"Kim","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.anireprosci.2014.09.002","article-title":"Characterization of pig sperm hyaluronidase and improvement of the digestibility of cumulus cell mass by recombinant pSPAM1 hyaluronidase in an in vitro fertilization assay","volume":"150","author":"Yoon","year":"2014","journal-title":"Anim. Reprod. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bbrc.2010.10.121","article-title":"Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking","volume":"403","author":"Kim","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14440","DOI":"10.1096\/fj.201900889RRR","article-title":"SPAM1\/HYAL5 double deficiency in male mice leads to severe male subfertility caused by a cumulus-oocyte complex penetration defect","volume":"33","author":"Park","year":"2019","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/ede.12285","article-title":"Pituitary adenylate cyclase-activating polypeptide in the testis of the quail Coturnix coturnix: Expression, localization, and phylogenetic analysis","volume":"21","author":"Prisco","year":"2019","journal-title":"Evol. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"113297","DOI":"10.1016\/j.ygcen.2019.113297","article-title":"Pituitary adenylate cyclase-activating peptide (PACAP) and its receptors in Mus musculus testis","volume":"286","author":"Prisco","year":"2020","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/jez.b.22896","article-title":"Seasonal expression and cellular distribution of star and steroidogenic enzymes in quail testis","volume":"332","author":"Rosati","year":"2019","journal-title":"J. Exp. Zool. B Mol. Dev. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"34957","DOI":"10.1074\/jbc.M314249200","article-title":"Possible function of the ADAM1a\/ADAM2 Fertilin complex in the appearance of ADAM3 on the sperm surface","volume":"279","author":"Nishimura","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1006\/dbio.2001.0462","article-title":"Calmegin is required for fertilin alpha\/beta heterodimerization and sperm fertility","volume":"240","author":"Ikawa","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1095\/biolreprod.106.052977","article-title":"Aberrant distribution of ADAM3 in sperm from both angiotensin-converting enzyme (Ace)- and calmegin (Clgn)-deficient mice","volume":"75","author":"Yamaguchi","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1002\/(SICI)1521-4141(199812)28:12<4094::AID-IMMU4094>3.0.CO;2-2","article-title":"CTX, a Xenopus thymocyte receptor, defines a molecular family conserved throughout vertebrates","volume":"28","author":"Chretien","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1074\/jbc.M308249200","article-title":"CLMP, a novel member of the CTX family and a new component of epithelial tight junctions","volume":"279","author":"Raschperger","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1530\/REP-13-0653","article-title":"Mice depleted of the coxsackievirus and adenovirus receptor display normal spermatogenesis and an intact blood-testis barrier","volume":"147","author":"Sultana","year":"2014","journal-title":"Reproduction."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"30310","DOI":"10.1074\/jbc.M204596200","article-title":"Mouse sperm lacking cell surface hyaluronidase PH-20 can pass through the layer of cumulus cells and fertilize the egg","volume":"277","author":"Baba","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18028","DOI":"10.1073\/pnas.0506825102","article-title":"Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass","volume":"102","author":"Kim","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1095\/biolreprod.109.078816","article-title":"Functional roles of mouse sperm hyaluronidases, HYAL5 and SPAM1, in fertilization","volume":"81","author":"Kimura","year":"2009","journal-title":"Biol. Reprod."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/4\/1037\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:34:10Z","timestamp":1760362450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/4\/1037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,7]]},"references-count":36,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ani11041037"],"URL":"https:\/\/doi.org\/10.3390\/ani11041037","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,7]]}}}