BIOMAT Database Logo BIOMAT Database Logo

A targeted glucocorticoid receptor antisense transgene increases thymocyte apoptosis and alters thymocyte development. 1995

L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health Bethesda, Maryland 20892, USA.

The exquisite sensitivity of thymocytes to steroid-induced apoptosis, the steroidogenic potential of thymic epithelial cells, and the ability of steroid synthesis inhibitors to enhance antigen-specific deletion of thymocytes in fetal thymic organ cultures suggest a role for glucocorticoids in thymocyte development. To address this further, transgenic mice that express antisense transcripts to the glucocorticoid receptor (GR) specifically in immature thymocytes were generated. The consequent hyporesponsiveness of thymocytes to glucocorticoids was accompanied by a reduction in thymic size, primarily owing to a decrease in the number of CD4+CD8+ cells. While an enhanced susceptibility to T cell receptor (TCR)-mediated apoptosis appeared to be partially responsible for this reduction, thymocyte loss could also be detected before thymocytes progressed to the CD4+CD8+ TCR alpha beta-expressing stage. These results suggest that glucocorticoids are necessary for survival and maturation of thymocytes, and are consistent with a role for steroids in both the transition from CD4-CD8- to CD4+CD8+ cells and the survival of CD4+CD8+ cells stimulated via the TCR.

UI MeSH Term Description Entries
D008297 Male Males
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009924 Organ Culture Techniques A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1) Organ Culture,Culture Technique, Organ,Culture Techniques, Organ,Organ Culture Technique,Organ Cultures
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D011965 Receptors, Glucocorticoid Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example. Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid

Related Publications

L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Thymocyte-targeted overexpression of xiap transgene disrupts T lymphoid apoptosis and maturation.
April 2001, Proceedings of the National Academy of Sciences of the United States of America,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Impaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene.
February 1992, Nature,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Interleukins modulate glucocorticoid-induced thymocyte apoptosis.
January 1992, International journal of clinical & laboratory research,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis.
March 1997, The Biochemical journal,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Progesterone inhibits glucocorticoid-induced murine thymocyte apoptosis.
November 2000, International journal of immunopharmacology,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
[Apoptosis and thymocyte development (epithelial cells as inducers of thymocyte apoptosis)].
January 1998, Izvestiia Akademii nauk. Seriia biologicheskaia,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Enhanced glucocorticoid receptor signaling in T cells impacts thymocyte apoptosis and adaptive immune responses.
March 2007, The American journal of pathology,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Prolactin suppresses glucocorticoid-induced thymocyte apoptosis in vivo.
May 2003, Endocrinology,
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Green fluorescent protein-glucocorticoid receptor knockin mice reveal dynamic receptor modulation during thymocyte development.
August 2002, Journal of immunology (Baltimore, Md. : 1950),
L B King, and M S Vacchio, and K Dixon, and R Hunziker, and D H Margulies, and J D Ashwell
Normal immune development and glucocorticoid-induced thymocyte apoptosis in mice deficient for the T-cell death-associated gene 8 receptor.
January 2006, Molecular and cellular biology,
Copied contents to your clipboard!