6533b853fe1ef96bd12acd61
RESEARCH PRODUCT
Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes, and c-kit-expressing lineage-negative hematopoietic cells
Cecilia AntunesCecilia AntunesCecilia AntunesSven BeilkeSven BeilkeSven BeilkeMichael CrossMichael CrossMichael CrossKatrin PresserKatrin PresserKatrin PresserRudiger AltRudiger AltRudiger AltBernd KainaBernd KainaBernd KainaSvetlana OhngemachSvetlana OhngemachSvetlana OhngemachUdo F. HartwigUdo F. HartwigUdo F. HartwigErnesto BockampSteffen SchmittSteffen SchmittSteffen SchmittMarko MaringerMarko MaringerMarko MaringerLeonid EshkindLeonid EshkindLeonid EshkindRolf SprengelRosario HeckRosario HeckRosario Hecksubject
MyeloidErythrocytesGenotypeTransgeneImmunologyMice TransgenicBiologyBiochemistryMiceMegakaryocyteGenes Reporterhemic and lymphatic diseasesProto-Oncogene ProteinsmedicineBasic Helix-Loop-Helix Transcription FactorsAnimalsT-Cell Acute Lymphocytic Leukemia Protein 1DNA PrimersRegulation of gene expressionReporter geneBase SequenceCell BiologyHematologyTetracyclineFlow CytometryMolecular biologyRecombinant ProteinsHematopoiesisHaematopoiesisProto-Oncogene Proteins c-kitmedicine.anatomical_structureGene Expression RegulationBone marrowStem cellMegakaryocytesGranulocytesdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-09-01 | Blood |