ArticleNucleic acids research1998
Stochastic, stage-specific mechanisms account for the variegation of a human globin transgene.
Article in Nucleic acids research, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
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- Generation of transgenic mouse fluorescent reporter lines for studying hematopoietic development.Methods in molecular biology (Clifton, N.J.) · 2014Article
- Identifying the initiating events of anti-Listeria responses using mice with conditional loss of IFN-γ receptor subunit 1 (IFNGR1).Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- A 3,387 bp 5'-flanking sequence of the goat alpha-S1-casein gene provides correct tissue-specific expression of human granulocyte colony-stimulating factor (hG-CSF) in the mammary gland of transgenic mice.Transgenic research · 2012Article
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- Dissection of platelet and myeloid cell defects by conditional targeting of the beta3-integrin subunit.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- p53-dependent transcription can exhibit both on/off and graded response after genotoxic stress.Oncogene · 2004Article
- Expression of the circadian clock gene Period 1 in neuroendocrine cells: an investigation using mice with a Per1::GFP transgene.The European journal of neuroscience · 2003Article
- Article
- Position effects are influenced by the orientation of a transgene with respect to flanking chromatin.Molecular and cellular biology · 2001Article
- Complex patterns of inheritance of an imprinted murine transgene suggest incomplete germline erasure.Nucleic acids research · 2000Article
- Enhancement of beta-globin locus control region-mediated transactivation by mitogen-activated protein kinases through stochastic and graded mechanisms.Molecular and cellular biology · 1999Article
- Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
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Authors and funding
7 authors.
Funding
Abstract
The random insertion of transgenes into the genomic DNA of mice usually leads to widely variable levels of expression in individual founder lines. To study the mechanisms that cause variegation, we designed a transgene that we expected to variegate, which consisted of a beta-globin locus control region 5' HS-2 linked in tandem to a tagged human beta-globin gene (into which a Lac-Z cassette had been inserted). All tested founder lines exhibited red blood cell-specific expression, but levels of expression varied >1000-fold from the lowest to the highest expressing line. Most of the variation in levels of expression appeared to reflect differences in the percentage of cells in the peripheral blood that expressed the transgene, which ranged from 0.3% in the lowest expressing line to 88% in the highest; the level of transgene expression per cell varied no more than 10-fold from the lowest to the highest expressing line. These differences in expression levels could not be explained by the location of transgene integration, by an effect of beta-galactosidase on red blood cell survival, by the half life of the beta-galactosidase enzyme or by the age of the animals. The progeny of all early erythroid progenitors (BFU-E colony-forming cells) exhibited the same propensity to variegate in methylcellulose-based cultures, suggesting that the decision to variegate occurs after the BFU-E stage of erythroid differentiation. Collectively, these data suggest that variegation in levels of transgene expression are due to local, integration site-dependent phenomena that alter the probability that a transgene will be expressed in an appropriate cell; however, these local effects have a minimal impact on the transgene's activity in the cells that initiate transcription.
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