title: Modulation of the murine CD8 gene complex following the targeted integration of human CD2-locus control region sequences.
abstract: 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.
authors: Division of Molecular Immunology, National Institute for Medical Research, Medical Research Council, London NW7 1AA, United Kingdom.
authors: Ursula
authors: U
authors: Menzel
authors: Theodoros
authors: T
authors: Kosteas
authors: Mauro
authors: M
authors: Tolaini
authors: Nigel
authors: N
authors: Killeen
authors: Kathleen
authors: K
authors: Roderick
authors: Dimitris
authors: D
authors: Kioussis
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D018801:CD2 Antigens / Q000235:genetics* / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D055879:Gene Knock-In Techniques; D006801:Humans; D019901:Locus Control Region / Q000235:genetics* / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D018801:CD2 Antigens; D016827:CD8 Antigens