{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:49:36Z","timestamp":1790675376166,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,12,23]]},"abstract":"<jats:p>\n                    Na\n                    <jats:sup>+<\/jats:sup>\n                    -independent anion exchangers (AE) mediate electroneutral exchange of Cl\n                    <jats:sup>-<\/jats:sup>\n                    for\n                    <jats:inline-formula>\n                      <jats:tex-math notation=\"LaTeX\">\\documentclass[12pt]{minimal}\n\\usepackage{amsmath}\n\\usepackage{wasysym} \n\\usepackage{amsfonts} \n\\usepackage{amssymb} \n\\usepackage{amsbsy}\n\\usepackage{mathrsfs}\n\\setlength{\\oddsidemargin}{-69pt}\n\\begin{document}\n\\begin{equation*}{\\mathrm{HCO}}_{3}^{-}\\end{equation*}\\end{document}<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    ions across cell membranes, being involved in intracellular pH and cell volume regulation and in transepithelial hydroionic fluxes. Bicarbonate activation of adenylyl cyclase is known to be necessary for sperm motility and sperm capacitation, and a few studies have suggested a possible role of AE carriers in reproduction. Among the four AE genes identified in mammals thus far, only\n                    <jats:italic>Ae2<\/jats:italic>\n                    (\n                    <jats:italic>Slc4a2<\/jats:italic>\n                    ) has been determined to be expressed in the male reproductive system, especially in developing spermatozoa and in epididymal epithelium. Most AE genes drive alternative transcription, which in mouse\n                    <jats:italic>Ae2<\/jats:italic>\n                    results in several Ae2 isoforms. Here, we generated mice carrying a targeted disruption of\n                    <jats:italic>Ae2<\/jats:italic>\n                    that prevents the expression of the three AE2 isoforms (Ae2a, Ae2b\n                    <jats:sub>1<\/jats:sub>\n                    , and Ae2b\n                    <jats:sub>2<\/jats:sub>\n                    ) normally found in mouse testes. Male\n                    <jats:italic>Ae2<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice (but not female\n                    <jats:italic>Ae2<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice) are infertile. Histopathological analysis of\n                    <jats:italic>Ae2<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    testes shows an interruption of spermiogenesis, with only a few late spermatids and a complete absence of spermatozoa in the seminiferous tubules. The number of apoptotic bodies is increased in the seminiferous tubules and in the epididymis, which also shows squamous metaplasia of the epididymal epithelium. Our findings reveal an essential role of\n                    <jats:italic>Ae2<\/jats:italic>\n                    in mouse spermiogenesis and stress the recently postulated involvement of bicarbonate in germ-cell differentiation through the bicarbonate-sensitive soluble-adenylyl-cyclase pathway.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2536127100","type":"journal-article","created":{"date-parts":[[2003,12,23]],"date-time":"2003-12-23T12:58:11Z","timestamp":1072184291000},"page":"15847-15852","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":70,"title":["Anion exchanger 2 is essential for spermiogenesis in mice"],"prefix":"10.1073","volume":"100","author":[{"given":"Juan F.","family":"Medina","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Recalde","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Prieto","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Lecanda","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"S\u00e1ez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin D.","family":"Funk","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vecino","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian A.","family":"van Roon","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roelof","family":"Ottenhoff","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piter J.","family":"Bosma","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conny T.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Division of Hepatology and Gene Therapy, University Hospital\/School of Medicine, Fundaci\u00f3n para la Investigaci\u00f3n Medica Aplicada, University of Navarra, E-31008 Pamplona, Spain; Center for Experimental Therapeutics, University of Pennsylvania, Biomedical Research Building II\/III, Philadelphia, PA 19104; Department of Cell Biology, University of the Basque Country, E-48940 Leioa, Spain; and Facility for Genetically Modified Mice and Laboratory for Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P. 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