{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:34:02Z","timestamp":1791239642733,"version":"4.1.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"40","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,10,4]]},"abstract":"<jats:p>\n                    Studies of chimeric mice demonstrated that the core Ig heavy chain (\n                    <jats:italic>IgH<\/jats:italic>\n                    ) intronic enhancer (iE\u03bc) functions in V(D)J and class switch recombination at the\n                    <jats:italic>IgH<\/jats:italic>\n                    locus. To more fully evaluate the role of this element in these and other processes, we generated mice homozygous for germ-line mutations in which the core sequences of iE\u03bc (cE\u03bc) were either deleted (cE\u03bc\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    mice) or replaced with a\n                    <jats:italic>\n                      pgk-Neo\n                      <jats:sup>R<\/jats:sup>\n                    <\/jats:italic>\n                    cassette (cE\u03bc\n                    <jats:sup>N\/N<\/jats:sup>\n                    mice). The cE\u03bc\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    mice had reduced B cell numbers, in association with impaired D to J\n                    <jats:sub>H<\/jats:sub>\n                    and V\n                    <jats:sub>H<\/jats:sub>\n                    to DJ\n                    <jats:sub>H<\/jats:sub>\n                    rearrangement, whereas cE\u03bc\n                    <jats:sup>N\/N<\/jats:sup>\n                    mice had a complete block in\n                    <jats:italic>IgH<\/jats:italic>\n                    V(D)J\n                    <jats:sub>H<\/jats:sub>\n                    recombination, confirming that additional cis elements cooperate with iE\u03bc to enforce D to J\n                    <jats:sub>H<\/jats:sub>\n                    recombination. In addition, developing cE\u03bc\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    and cE\u03bc\n                    <jats:sup>N\/N<\/jats:sup>\n                    B lineage cells had correspondingly decreased levels of germ-line transcripts from the J\n                    <jats:sub>H<\/jats:sub>\n                    region of the\n                    <jats:italic>IgH<\/jats:italic>\n                    locus (\u03bc0 and I\u03bc transcripts); although both had normal levels of germ-line V\n                    <jats:sub>H<\/jats:sub>\n                    transcripts, suggesting that cE\u03bc may influence\n                    <jats:italic>IgH<\/jats:italic>\n                    locus V(D)J recombination by influencing accessibility of J\n                    <jats:sub>H<\/jats:sub>\n                    proximal regions of the locus. Consistent with chimera studies, peripheral cE\u03bc\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    B cells had normal surface Ig and relatively normal class switch recombination. However, cE\u03bc\n                    <jats:sup>\u0394\/\u0394<\/jats:sup>\n                    B cells also had relatively normal somatic hypermutation of their\n                    <jats:italic>IgH<\/jats:italic>\n                    variable region genes, showing unexpectedly that the cE\u03bc is not required for this process. The availability of mice with the iE\u03bc mutation in their germ line will facilitate future studies to elucidate the roles of iE\u03bc in V\n                    <jats:sub>H<\/jats:sub>\n                    (D)J\n                    <jats:sub>H<\/jats:sub>\n                    recombination in the context of\n                    <jats:italic>IgH<\/jats:italic>\n                    chromatin structure and germ-line transcription.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0507090102","type":"journal-article","created":{"date-parts":[[2005,9,26]],"date-time":"2005-09-26T20:35:00Z","timestamp":1127766900000},"page":"14362-14367","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":171,"title":["Elucidation of IgH intronic enhancer functions via germ-line deletion"],"prefix":"10.1073","volume":"102","author":[{"given":"Thomas","family":"Perlot","sequence":"first","affiliation":[{"name":"The CBR Institute for Biomedical Research, Inc., and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; Howard Hughes Medical Institute, Children's Hospital, 1 Blackfan Circle, Boston, MA 02115; and University of Vienna, Dr.-Karl-Lueger-Ring1, A-1010 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick W.","family":"Alt","sequence":"additional","affiliation":[{"name":"The CBR Institute for Biomedical Research, Inc., and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; Howard Hughes Medical Institute, Children's Hospital, 1 Blackfan Circle, Boston, MA 02115; and University of Vienna, Dr.-Karl-Lueger-Ring1, A-1010 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig H.","family":"Bassing","sequence":"additional","affiliation":[{"name":"The CBR Institute for Biomedical Research, Inc., and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; Howard Hughes Medical Institute, Children's Hospital, 1 Blackfan Circle, Boston, MA 02115; and University of Vienna, Dr.-Karl-Lueger-Ring1, A-1010 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikyung","family":"Suh","sequence":"additional","affiliation":[{"name":"The CBR Institute for Biomedical Research, Inc., and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; Howard Hughes Medical Institute, Children's Hospital, 1 Blackfan Circle, Boston, MA 02115; and University of Vienna, Dr.-Karl-Lueger-Ring1, A-1010 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pinaud","sequence":"additional","affiliation":[{"name":"The CBR Institute for Biomedical Research, Inc., and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; Howard Hughes Medical Institute, Children's Hospital, 1 Blackfan Circle, Boston, MA 02115; and University of Vienna, 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