Basigin null mutant male mice are sterile and exhibit impairedinteractions between germ cells and Sertoli cellsJiajia Bia, Yanfen Lia, Fengyun Sunb, Anja Saalbachc, Claudia Kleinc, David J. Millera,Rex Hessd, Romana A. Nowaka,naDepartment of Animal Sciences, University of Illinois, Urbana, IL, USAbThe Jackson Laboratory, Bar Harbor, Maine, ME, USAcDepartment of Dermatology, Venereology and Allergology, Leipzig University, Leipzig, GermanydDepartment of Comparative Biosciences, University of Illinois, Urbana, IL, USAa r t i c l e i n f oArticle history:Received 27 September 2012Received in revised form10 May 2013Accepted 14 May 2013Available online 28 May 2013Keywords:BasiginBSGN-glycansα-Mannosidase IISpermatogenesisBlood-testis barriera b s t r a c tBasigin (BSG) is a multifunctional glycoprotein that plays an important role in male reproduction sincemale knockout (KO) mice are sterile. The Bsg KO testis lacks elongated spermatids and maturespermatozoa, a phenotype similar to that of alpha-mannosidase IIx (MX) KO mice. MX regulatesformation of N-acetylglucosamine (GlcNAc) terminated N-glycans that participate in germ cell-Sertolicell adhesion. Results showed that Bsg KO spermatocytes displayed normal homologous chromosomesynapsis and progression through meiosis. However, only punctate expression of the round spermatidmarker SP-10 in the acrosomal granule of germ cells of Bsg KO mice was detected indicating thatspermatogenesis in Bsg KO mice was arrested at the early round spermatid stages. We observed a largeincrease in the number of germ cells undergoing apoptosis in Bsg KO testes. Using lectin blotting, wedetermined that GlcNAc terminated N-glycans are linked to BSG. GlcNAc terminated N-glycans weresignificantly reduced in Bsg KO testes. These observations indicate that BSG may act as a germ cell-Sertolicell attachment molecule. Loss of BSG significantly reduced adhesion between GC-2 and SF7 cells.Moreover, wild type testes showed strong expression of N-cadherin (CDH2) while expression was greatlyreduced in the testes of Bsg KO mice. In addition, the integrity of the blood-testis barrier (BTB) wascompromised in Bsg KO testes. In conclusion, although some Bsg KO spermatogonia can undergo normalprogression to the spermatocyte stage, BSG-mediated germ cell-Sertoli cell interactions appear to benecessary for integrity of the BTB and spermatocyte progression to mature spermatozoa.& 2013 Elsevier Inc. All rights reserved.IntroductionSpermatogenesis is the process of producing sperm (haploid)from initially undifferentiated spermatogonia (diploid). Duringspermatogenesis, there are a group of somatic cells named Sertolicells that have direct contact with all the different types of germcells in the seminiferous tubules. Sertoli cells play a major role inthe regulation of germ cell differentiation and migration. First,these cells form the blood-testis barrier (BTB) in the seminiferousepithelium near the basement membrane which protects thepostmeiotic germ cells from the host immune system in order toavoid attack from the production of anti-sperm antibodies againstgerm cell specific antigens (Dym and Fawcett, 1970; Morrow et al.,2009; Wong et al., 2010). The BTB has been shown to be composedof tight junctions (TJ), basal ectoplasmic specializations (basal ES,a testis-specific type of adherens junction), gap junctions (GJ)anddesmosome-likejunctions.Severaladhesionmoleculeshave been identified to play an important role in the functioningof these junctions including claudins and occludins (TJ); cox-sacckie and adenovirus receptor (CXADR), N-cadherin (CDH2)and β-catenin (basal ES); connexin43 (CX43) (GJ); desmoglein-2and desmocollin-2 (desmosome-like junction) (Cheng and Mruk,2009; Komljenovic et al., 2009; Pointis and Segretain, 2005; Wonget al., 2008). Knockouts generated against specific junction pro-teins such as claudin 11 (CLDN11) (Gow et al., 1999) can causesterility in the male mouse, which emphasizes the role thesejunction proteins play in the appropriate functioning of the BTBand also prove that an intact BTB is necessary for successful malefertility.Sertoli cells are also responsible for the formation and secretionof seminiferous tubule fluid (STF) which consists of a number ofproducts that are involved in spermatogenesis such as transportand binding proteins, proteases and protease inhibitors, hormonesand growth factors (Russell and Griswold, 1993; Skinner andContents lists available at SciVerse ScienceDirectjournal homepage: www.elsevier.com/locate/developmentalbiologyDevelopmental Biology0012-1606/$-see front matter & 2013 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.ydbio.2013.05.023nCorrespondence to: 1207 W Gregory Dr. Urbana, IL 61801. Fax: +217 333 8286.E-mail address: ranowak@illinois.edu (R.A. Nowak).Developmental Biology 380 (2013) 145–156
