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The VpreB1 enhancer drives developmental stage-specific gene expression in vivo

Licence, S; Persson, Christine LU ; Mundt, C and Martensson, IL (2003) In European Journal of Immunology 33(4). p.1117-1126
Abstract
In adult mice, the VpreB genes are expressed in bone marrow progenitor (pro-) and precursor (pre-) B cells. As part of the pre-B cell receptor, the proteins are crucial for the proliferation of these cells and consequently normal B lymphocyte development. Using cell lines, we identified a lineage- and developmental-stage-specific VpreB1 enhancer. Here, we analyze its specificity in vivo by generating transgenic mice in which expression of a reporter gene (human CD122) is regulated by the VpreB1 enhancer in the context of its own promoter. All transgenic lines expressed the reporter gene in the bone marrow in a copy number-independent manner, whereas expression levels were integration site-dependent. While the enhancer is not tissue... (More)
In adult mice, the VpreB genes are expressed in bone marrow progenitor (pro-) and precursor (pre-) B cells. As part of the pre-B cell receptor, the proteins are crucial for the proliferation of these cells and consequently normal B lymphocyte development. Using cell lines, we identified a lineage- and developmental-stage-specific VpreB1 enhancer. Here, we analyze its specificity in vivo by generating transgenic mice in which expression of a reporter gene (human CD122) is regulated by the VpreB1 enhancer in the context of its own promoter. All transgenic lines expressed the reporter gene in the bone marrow in a copy number-independent manner, whereas expression levels were integration site-dependent. While the enhancer is not tissue specific, within the B cell lineage the expression pattern of human CID122 mimicked that of endogenous VpreB1. Thus, low levels were detected in pro-B cells, high levels in pre-BI and slightly lower levels in pre-BII cells; no expression was detected in immature/mature B cells. Furthermore, when in vitro cultured transgenic pre-B cells differentiated into immature B cells there was concomitant down-regulation of human CD122 and endogenous VpreB1. Thus the VpreB1 enhancer is sufficient to ensure developmental stage-specific expression of a reporter gene in B lymphocytes in vivo. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pre-B cell, surrogate light chain, VpreB, enhancer
in
European Journal of Immunology
volume
33
issue
4
pages
1117 - 1126
publisher
John Wiley & Sons
external identifiers
  • wos:000182186500032
  • pmid:12672078
  • scopus:0038744372
ISSN
1521-4141
DOI
language
English
LU publication?
yes
id
9e528209-0aa6-4f4b-9375-2b1370c308c3 (old id 313779)
date added to LUP
2007-09-16 12:12:09
date last changed
2018-05-29 12:06:48
@article{9e528209-0aa6-4f4b-9375-2b1370c308c3,
  abstract     = {In adult mice, the VpreB genes are expressed in bone marrow progenitor (pro-) and precursor (pre-) B cells. As part of the pre-B cell receptor, the proteins are crucial for the proliferation of these cells and consequently normal B lymphocyte development. Using cell lines, we identified a lineage- and developmental-stage-specific VpreB1 enhancer. Here, we analyze its specificity in vivo by generating transgenic mice in which expression of a reporter gene (human CD122) is regulated by the VpreB1 enhancer in the context of its own promoter. All transgenic lines expressed the reporter gene in the bone marrow in a copy number-independent manner, whereas expression levels were integration site-dependent. While the enhancer is not tissue specific, within the B cell lineage the expression pattern of human CID122 mimicked that of endogenous VpreB1. Thus, low levels were detected in pro-B cells, high levels in pre-BI and slightly lower levels in pre-BII cells; no expression was detected in immature/mature B cells. Furthermore, when in vitro cultured transgenic pre-B cells differentiated into immature B cells there was concomitant down-regulation of human CD122 and endogenous VpreB1. Thus the VpreB1 enhancer is sufficient to ensure developmental stage-specific expression of a reporter gene in B lymphocytes in vivo.},
  author       = {Licence, S and Persson, Christine and Mundt, C and Martensson, IL},
  issn         = {1521-4141},
  keyword      = {pre-B cell,surrogate light chain,VpreB,enhancer},
  language     = {eng},
  number       = {4},
  pages        = {1117--1126},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {The VpreB1 enhancer drives developmental stage-specific gene expression in vivo},
  url          = {http://dx.doi.org/},
  volume       = {33},
  year         = {2003},
}