{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T02:46:26Z","timestamp":1778121986760,"version":"3.51.4"},"reference-count":54,"publisher":"Proceedings of the National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,10,29]]},"abstract":"<jats:p>\n            The\n            <jats:italic>toothless<\/jats:italic>\n            (\n            <jats:italic>tl<\/jats:italic>\n            ) mutation in the rat is a naturally occurring, autosomal recessive mutation resulting in a profound deficiency of bone-resorbing osteoclasts and peritoneal macrophages. The failure to resorb bone produces severe, unrelenting osteopetrosis, with a highly sclerotic skeleton, lack of marrow spaces, failure of tooth eruption, and other pathologies. Injections of CSF-1 improve some, but not all, of these. In this report we have used polymorphism mapping, sequencing, and expression studies to identify the genetic lesion in the\n            <jats:italic>tl<\/jats:italic>\n            rat. We found a 10-base insertion near the beginning of the open reading of the\n            <jats:italic>Csf1<\/jats:italic>\n            gene that yields a truncated, nonfunctional protein and an early stop codon, thus rendering the\n            <jats:italic>tl<\/jats:italic>\n            rat CSF-1\n            <jats:sup>\n              <jats:italic>null<\/jats:italic>\n            <\/jats:sup>\n            . All mutants were homozygous for the mutation and all carriers were heterozygous. No CSF-1 transcripts were identified in rat mRNA that would avoid the mutation via alternative splicing. The biology and actions of CSF-1 have been elucidated by many studies that use another naturally occurring mutation, the\n            <jats:italic>op<\/jats:italic>\n            mouse, in which a single base insertion also disrupts the reading frame. The\n            <jats:italic>op<\/jats:italic>\n            mouse has milder osteoclastopenia and osteopetrosis than the\n            <jats:italic>tl<\/jats:italic>\n            rat and recovers spontaneously over the first few months of life. Thus, the\n            <jats:italic>tl<\/jats:italic>\n            rat provides a second model in which the functions of CSF-1 can be studied. Understanding the similarities and differences in the phenotypes of these two models will be important to advancing our knowledge of the many actions of CSF-1.\n          <\/jats:p>","DOI":"10.1073\/pnas.202332999","type":"journal-article","created":{"date-parts":[[2002,10,29]],"date-time":"2002-10-29T17:24:11Z","timestamp":1035912251000},"page":"14303-14308","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":114,"title":["The osteopetrotic mutation\n            <i>toothless<\/i>\n            (\n            <i>tl<\/i>\n            ) is a loss-of-function frameshift mutation in the rat\n            <i>Csf1<\/i>\n            gene: Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification"],"prefix":"10.1073","volume":"99","author":[{"given":"Liesbeth","family":"Van Wesenbeeck","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, Antwerp B-2610, Belgium; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R.","family":"Odgren","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, Antwerp B-2610, Belgium; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole A.","family":"MacKay","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, Antwerp B-2610, Belgium; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"D'Angelo","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, Antwerp B-2610, Belgium; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fayez F.","family":"Safadi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, Antwerp B-2610, Belgium; Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue, North Worcester, MA 01655; and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven N.","family":"Popoff","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, Antwerp B-2610, Belgium; 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