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Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival

Corcoran, Lynn M. and Karvelas, Maria and Nossal, G. J. V. and Ye, Zheng-Sheng and Jacks, Tyler and Baltimore, David (1993) Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival. Genes and Development, 7 (4). pp. 570-582. ISSN 0890-9369.

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Oct-2, a POU homeo domain transcription factor, is believed to stimulate B-cell-restricted expression of immunoglobulin genes through binding sites in immunoglobulin gene promoters and enhancers. To determine whether Oct-2 is required for B-cell development or function, or has other developmental roles, the gene was disrupted by homologous recombination. Oct-2^(-/-) mice develop normally but die within hours of birth for undetermined reasons. Mutants contain normal numbers of B-cell precursors but are somewhat deficient in IgM+ B cells. These B cells have a marked defect in their capacity to secrete immunoglobulin upon mitogenic stimulation in vitro. Thus, Oct-2 is not required for the generation of immunoglobulin-bearing B cells but is crucial for their maturation to immunoglobulin-secreting cells and for another undetermined organismal function.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1993 by Cold Spring Harbor Laboratory Press. Received January 13, 1993; revised version accepted February 1, 1993. We are grateful to the following people for reagents: D. Gearing [leukemia inhibitory factor (LIF)], R. Jaenisch (D3 cells), T. Wirth (anti-Oct-2 antibodies), P. Jackson (A-MuLV), A. Strasser (monoclonal antibodies and 3T3/IL-7 cells), A. Winoto (genomic library), and A. Kudo, F. Melchers, R. Wall, R. Grosschedl, F. Alt, and M. Schlissel (eDNA probes). D. Metcalf performed analysis of myeloid lineages and commented on histology, as did S. Cheema and P. Waring. J. Dausman and M. Rudnicki provided guidance on production of mutant mice, and T. Baldwin and L. Weiher cared for animals. We also thank J. Adams, S. Cory, and A. Harris for commenting on the manuscript. L.C. was supported by the Glaxo Corporation, through the Life Science Research Foundation, and is currently a Cancer Research Institute investigator. M.K. and G.N. were supported by the National Institutes of Health (grant AI-03958) and a Human Frontier Science Program grant (principal investigator, K. Rajewsky). Z-S.Y. received a postdoctoral fellowship from the Leukemia Society, and T.J. is a Lucille P. Markey scholar. This work was also supported by a U.S. Public Health Service Grant (GM39458) to D.B. and by the Australian National Health and Medical Research Council. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.
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Glaxo CorporationUNSPECIFIED
Life Science Research FoundationUNSPECIFIED
Cancer Research InstituteUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Leukemia Society of AmericaUNSPECIFIED
Lucille P. Markey Charitable TrustUNSPECIFIED
Australian National Health and Medical Research Council (NHMRC)UNSPECIFIED
Subject Keywords:Oct-2; POU homeo domain; B-cell development; immunoglobulin genes
Issue or Number:4
Record Number:CaltechAUTHORS:20200513-145713907
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103187
Deposited By: Tony Diaz
Deposited On:13 May 2020 22:16
Last Modified:13 May 2020 22:16

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