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Publication : Modulation of the murine CD8 gene complex following the targeted integration of human CD2-locus control region sequences.

First Author  Menzel U Year  2011
Journal  J Immunol Volume  187
Issue  7 Pages  3712-20
PubMed ID  21880987 Mgi Jnum  J:179326
Mgi Id  MGI:5301785 Doi  10.4049/jimmunol.1100709
Citation  Menzel U, et al. (2011) Modulation of the murine CD8 gene complex following the targeted integration of human CD2-locus control region sequences. J Immunol 187(7):3712-20
abstractText  The human CD2 (hCD2) locus control region (LCR) inserted in the mouse CD8 gene complex activates expression of the CD8 genes in T cell subsets in which the CD8 locus is normally silenced (e.g., CD4(+) single-positive T cells). In this article, we show that, in conditional mCD8/hCD2-LCR (CD8/LCR) knock-in mice, the continuous presence of the hCD2-LCR is required for this effect. Deletion of the inserted hCD2-LCR in a developmental stage and cell lineage-specific manner revealed that the temporary presence of the LCR during early development does not permanently alter the expression pattern of the CD8 genes. As a result, cells that have been affected by the insertion of the LCR can convert to their destined phenotype once the LCR is removed. DNaseI hypersensitive sites 1 and 2 of the hCD2-LCR influence the expression of the CD8 genes in a similar manner as does the full LCR, whereas insertion of hypersensitive site 3 alone of the LCR does not result in a changed expression pattern. This analysis revealed a dynamic interaction between the hCD2-LCR and the endogenous regulatory elements of the CD8 genes.
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