Fate Mapping for Activation-Induced Cytidine Deaminase (AID) Marks Non-Lymphoid Cells During Mouse Development

被引:20
作者
Rommel, Philipp C. [1 ]
Bosque, David [1 ]
Gitlin, Alexander D. [1 ]
Croft, Gist F. [2 ]
Heintz, Nathaniel [3 ,4 ]
Casellas, Rafael [5 ,6 ]
Nussenzweig, Michel C. [1 ,4 ]
Kriaucionis, Skirmantas [3 ,7 ,8 ]
Robbiani, Davide F. [1 ]
机构
[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA
[2] Rockefeller Univ, Lab Mol Vertebrate Embryol, New York, NY 10021 USA
[3] Rockefeller Univ, Mol Biol Lab, New York, NY 10021 USA
[4] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[5] NIAMS, Bethesda, MD USA
[6] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[7] Ludwig Inst Canc Res, Oxford, England
[8] Univ Oxford, Oxford, England
基金
美国国家卫生研究院;
关键词
CLASS SWITCH RECOMBINATION; B-CELL; SOMATIC HYPERMUTATION; EMBRYONIC LETHALITY; DNA; TRANSLOCATIONS; DEFICIENCY; MICE; MEDULLOBLASTOMAS; INACTIVATION;
D O I
10.1371/journal.pone.0069208
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Aicda gene encodes Activation-Induced cytidine Deaminase (AID), an enzyme essential for remodeling antibody genes in mature B lymphocytes. AID is also responsible for DNA damage at oncogenes, leading to their mutation and cancer-associated chromosome translocation in lymphoma. We used fate mapping and AID(GFP) reporter mice to determine if AID expression in the mouse extends beyond lymphocytes. We discovered that AID(cre) tags a small fraction of non-lymphoid cells starting at 10.5 days post conception (dpc), and that AID(GFP+) cells are detectable at dpc 11.5 and 12.5. Embryonic cells are tagged by AID(cre) in the submandibular region, where conditional deletion of the tumor suppressor PTEN causes squamous papillomas. AID(cre) also tags non-lymphoid cells in the embryonic central nervous system. Finally, in the adult mouse brain, AID(cre) marks a small fraction of diverse neurons and distinct neuronal populations, including pyramidal cells in cortical layer IV.
引用
收藏
页数:9
相关论文
共 48 条
[1]   Regulation of AID expression in the immune response [J].
Crouch, Elizabeth E. ;
Li, Zhiyu ;
Takizawa, Makiko ;
Fichtner-Feigl, Stefan ;
Gourzi, Polyxeni ;
Montano, Carolina ;
Feigenbaum, Lionel ;
Wilson, Patrick ;
Janz, Siegfried ;
Papavasiliou, F. Nina ;
Casellas, Rafael .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (05) :1145-1156
[2]   Molecular mechanisms of antibody somatic hypermutation [J].
Di Nola, Javier M. ;
Neuberger, Michael S. .
ANNUAL REVIEW OF BIOCHEMISTRY, 2007, 76 :1-22
[3]   MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation [J].
Dorsett, Yair ;
McBride, Kevin M. ;
Jankovic, Mila ;
Gazumyan, Anna ;
Thai, To-Ha ;
Robbiani, Davide F. ;
Di Virgilio, Michela ;
San-Martin, Bernardo Reina ;
Heidkamp, Gordon ;
Schwickert, Tanja A. ;
Eisenreich, Thomas ;
Rajewsky, Klaus ;
Nussenzweig, Michel C. .
IMMUNITY, 2008, 28 (05) :630-638
[4]   Late embryonic lethality and impaired V(D)J recombination in mice lacking DNA ligase IV [J].
Frank, KM ;
Sekiguchi, JM ;
Seidl, KJ ;
Swat, W ;
Rathbun, GA ;
Cheng, HL ;
Davidson, L ;
Kangaloo, L ;
Alt, FW .
NATURE, 1998, 396 (6707) :173-177
[5]   DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway [J].
Frank, KM ;
Sharpless, NE ;
Gao, YJ ;
Sekiguchi, JM ;
Ferguson, DO ;
Zhu, CM ;
Manis, JP ;
Horner, J ;
DePinho, RA ;
Alt, FW .
MOLECULAR CELL, 2000, 5 (06) :993-1002
[6]   Recurrent genomic alterations characterize medulloblastoma arising from DNA double-strand break repair deficiency [J].
Frappart, Pierre-Olivier ;
Lee, Youngsoo ;
Russell, Helen R. ;
Chalhoub, Nader ;
Wang, Yong-Dong ;
Orii, Kenji E. ;
Zhao, Jingfeng ;
Kondo, Naomi ;
Baker, Suzanne J. ;
McKinnon, Peter J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (06) :1880-1885
[7]   Cytidine deaminases: AIDing DNA demethylation? [J].
Fritz, Eric L. ;
Papavasiliou, F. Nina .
GENES & DEVELOPMENT, 2010, 24 (19) :2107-2114
[8]   Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development [J].
Gao, YJ ;
Ferguson, DO ;
Xie, W ;
Manis, JP ;
Sekiguchi, J ;
Frank, KM ;
Chaudhuri, J ;
Horner, J ;
DePinho, RA ;
Alt, FW .
NATURE, 2000, 404 (6780) :897-900
[9]   A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis [J].
Gao, YJ ;
Sun, Y ;
Frank, KM ;
Dikkes, P ;
Fujiwara, Y ;
Seidl, KJ ;
Sekiguchi, JM ;
Rathbun, GA ;
Swat, W ;
Wang, JY ;
Bronson, RT ;
Malynn, BA ;
Bryans, M ;
Zhu, CM ;
Chaudhuri, J ;
Davidson, L ;
Ferrini, R ;
Stamato, T ;
Orkin, SH ;
Greenberg, ME ;
Alt, FW .
CELL, 1998, 95 (07) :891-902
[10]   Mechanisms that Promote and Suppress Chromosomal Translocations in Lymphocytes [J].
Gostissa, Monica ;
Alt, Frederick W. ;
Chiarle, Roberto .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :319-350