title: Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes, and c-kit-expressing lineage-negative hematopoietic cells.
abstract: The stem cell leukemia gene SCL, also known as TAL-1, encodes a basic helix-loop-helix transcription factor expressed in erythroid, myeloid, megakaryocytic, and hematopoietic stem cells. To be able to make use of the unique tissue-restricted and spatio-temporal expression pattern of the SCL gene, we have generated a knock-in mouse line containing the tTA-2S tetracycline transactivator under the control of SCL regulatory elements. Analysis of this mouse using different tetracycline-dependent reporter strains demonstrated that switchable transgene expression was restricted to erythrocytes, megakaryocytes, granulocytes, and, importantly, to the c-kit-expressing and lineage-negative cell fraction of the bone marrow. In addition, conditional transgene activation also was detected in a very minor population of endothelial cells and in the kidney. However, no activation of the reporter transgene was found in the brain of adult mice. These findings suggested that the expression of tetracycline-responsive reporter genes recapitulated the known endogenous expression pattern of SCL. Our data therefore demonstrate that exogenously inducible and reversible expression of selected transgenes in myeloid, megakaryocytic, erythroid, and c-kit-expressing lineage-negative bone marrow cells can be directed through SCL regulatory elements. The SCL knock-in mouse presented here represents a powerful tool for studying normal and malignant hematopoiesis in vivo.
authors: Institute of Toxicology/Mouse Genetics, Johannes Gutenberg-Universität Mainz, Obere Zahlbacher Str 67, 55131 Mainz, Germany. bockamp@mail.uni-mainz.de
authors: Ernesto
authors: E
authors: Bockamp
authors: Cecilia
authors: C
authors: Antunes
authors: Marko
authors: M
authors: Maringer
authors: Rosario
authors: R
authors: Heck
authors: Katrin
authors: K
authors: Presser
authors: Sven
authors: S
authors: Beilke
authors: Svetlana
authors: S
authors: Ohngemach
authors: Rudiger
authors: R
authors: Alt
authors: Michael
authors: M
authors: Cross
authors: Rolf
authors: R
authors: Sprengel
authors: Udo
authors: U
authors: Hartwig
authors: Bernd
authors: B
authors: Kaina
authors: Steffen
authors: S
authors: Schmitt
authors: Leonid
authors: L
authors: Eshkind