Disease relevance of Rorc

• Rorgamma (Rorc) is a common integration site in type B leukemogenic virus-induced T-cell lymphomas [1].
• Thorp and Gallagher first reported that depletion of cholesterol inhibited virus entry and cell-cell fusion of mouse hepatitis virus (MHV), suggesting the importance of lipid rafts in MHV replication (E. B. Thorp and T. M. Gallagher, J. Virol. 78:2682-2692, 2004) [2].
• Two human gastric cancers, WIL and TOR, were transplanted subcutaneously into athymic nude mice [3].
• In sham-treated mice lacking RORgamma, low-grade pulmonary inflammation was observed and characterized by the perivascular accumulation of B and T lymphocytes, increased numbers of inflammatory cells in the lung lavage fluid, and polyclonal Ig activation [4].
• Double deficiencies in ROR alpha and ROR gamma globally impaired Th17 generation and completely protected mice against experimental autoimmune encephalomyelitis [5].

High impact information on Rorc

• Hence, RORgamma has critical functions in T cell repertoire selection and lymphoid organogenesis [6].
• RORgamma was also required for development of lymph nodes and Peyer's patches, but not splenic follicles [6].
• Mixed radiation bone marrow chimeras revealed that RORgamma functions in an iNKT cell lineage-specific manner [7].
• The thymus of RORgamma(-/-) mice contains 74.4% +/- 8.9% fewer thymocytes than that of wild-type mice [8].
• To identify the physiological functions of the retinoid-related orphan receptor gamma (RORgamma), a member of the nuclear receptor superfamily, mice deficient in RORgamma function were generated by targeted disruption [8].

Chemical compound and disease context of Rorc

• High incidence of T-cell lymphomas in mice deficient in the retinoid-related orphan receptor RORgamma [9].

Biological context of Rorc

• Our findings support a model in which RORgamma negatively controls apoptosis in thymocytes [8].
• Flow cytometric analysis demonstrated a 6-fold rise in the percentage of cells in the S phase of the cell cycle among thymocytes from RORgamma(-/-) mice [8].
• In addition to the thynic phenotype, RORgamma-/- mice lack lymph nodes, indicating that RORgamma is essential for lymph node organogenesis [10].
• Collectively, these results suggest that RORgamma regulates lymphocyte homeostasis at multiple levels [11].
• Our data suggest that down-regulation of ROR gamma t expression in thymocytes is essential for their maturation [12].

Anatomical context of Rorc

• RORgamma is also required for the development of lymph nodes and Peyer's patches [13].
• RORgamma(-/-) mice lack peripheral and mesenteric lymph nodes and Peyer's patches, indicating that RORgamma expression is indispensable for lymph node organogenesis [8].
• However, RORgamma(-/-) mice have 2- to 3-fold more splenocytes than wild-type controls due to an accumulation of conventional resting B lymphocytes [11].
• Evidence that cyclin D1 mediates both growth and proliferation downstream of TOR in hepatocytes [14].
• Induction of the nuclear orphan receptor RORgamma during adipocyte differentiation of D1 and 3T3-L1 cells [15].

Associations of Rorc with chemical compounds

• Retinoid-related orphan receptor gamma (RORgamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis [8].
• The hormone nuclear receptor retinoic acid receptor-related orphan receptor gamma (RORgamma) plays important roles in thymocyte development and lymphoid organogenesis [11].
• TOR: a new orphan receptor expressed in the thymus that can modulate retinoid and thyroid hormone signals [16].
• Thus, TOR is part of a subgroup of receptors, one of which has recently been reported to be activated by melatonin [16].
• In contrast to parental cells, clofibrate induces adipogenesis and RORalpha and RORgamma mRNA in BALB/c3T3 cells that ectopically express PPARgamma [15].

Regulatory relationships of Rorc

• The ROR gamma t transgene inhibits IL-2 production by mature T cells, and this inhibition may be partially due to the inhibitory effect of ROR gamma t on c-Rel transcription [12].
• Like the expression of PPARgamma and aP2, the induction of RORgamma mRNA was repressed by tumor necrosis factor alpha and transforming growth factor beta [15].

Other interactions of Rorc

• In contrast, mammalian TOR kinase activity has been reported to be regulated by growth factor stimulation via the PI3K/Akt pathway [17].
• Therefore, our data suggest that TOR, similar to COUP-TF, can negatively regulate retinoic acid and thyroid hormone signals [16].
• TOR, however, is able to repress TR and RAR activity on DR-4-TREs or DR-5-RAREs, respectively [16].
• This orphan receptor, referred to as ROR gamma, belongs to the ROR/RZR subfamily [18].
• Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining demonstrated a 4-fold increase in apoptotic cells in the cortex of the thymus of RORgamma(-/-) mice [8].

Analytical, diagnostic and therapeutic context of Rorc

• We show by fluorescence in situ hybridization that the mouse ROR gamma gene is located on chromosome 3, in a region that corresponds to band 3F2.1-2 [19].
• Northern blot analysis using RNA from multiple tissues indicated that ROR gamma is expressed in several tissues but is most highly expressed in skeletal muscle [18].
• Microarray analysis was performed in order to uncover differences in gene expression between thymocytes of wild-type and RORgamma-/- mice [20].

References