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To test this hypothesis we generated and analyzed dCK knockout (KO) mice. dCK inactivation selectively and profoundly affected T and B cell development. A 90-fold decrease in thymic cellularity was observed in the dCK KO mice relative to wild-type littermates. Lymphocyte numbers in the dCK KO mice were 5- to 13-fold below normal values. The severe impact of dCK inactivation on lymphopoiesis was unexpected given that nucleoside salvage has been thought to play a limited, \"fine-tuning\" role in regulating deoxyribonucleotide triphosphate pools produced by the de novo pathway. The dCK KO phenotype challenges this view and indicates that, in contrast to the great majority of other somatic cells, normal lymphocyte development critically requires the deoxyribonucleoside salvage pathway.<\/jats:p>","DOI":"10.1073\/pnas.0913900107","type":"journal-article","created":{"date-parts":[[2009,12,31]],"date-time":"2009-12-31T20:13:56Z","timestamp":1262290436000},"page":"5551-5556","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["Requirement for deoxycytidine kinase in T and B lymphocyte development"],"prefix":"10.1073","volume":"107","author":[{"given":"Gerald","family":"Toy","sequence":"first","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Crump Institute for Molecular Imaging,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne R.","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Crump Institute for Molecular Imaging,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-I","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Crump Institute for Molecular Imaging,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Cheng","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean O.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Crump Institute for Molecular Imaging,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomo-o","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn W.","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagichettiar","family":"Satyamurthy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Phelps","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey R.","family":"Herschman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Crump Institute for Molecular Imaging,"},{"name":"Department of Biological Chemistry, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Czernin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Ahmanson Biological Imaging Division, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen N.","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology,"},{"name":"Howard Hughes Medical Institute,"},{"name":"Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; 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