Disease relevance of Nr1d2

• beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity [1].

Psychiatry related information on Nr1d2

• beta-Amyloid peptides (Abeta40 and Abeta42) are the major constituents of amyloid plaques, which are one of the hallmarks of Alzheimer's disease (AD) [2].

High impact information on Nr1d2

• beta adrenoceptor (betaAR) signaling is finely regulated to mediate the sympathetic nervous system control of cardiovascular function [3].
• beta -Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulation [4].
• This decrease in RVR mRNA correlated with the appearance of muscle-specific markers (e.g. myogenin mRNA) [5].
• Since other 'orphans', e.g. COUP-TF II and Rev-erbA alpha, have been demonstrated to regulate muscle and adipocyte differentiation, we investigated the expression and functional role of RVR during mouse myogenesis [5].
• In conclusion, our studies identified a potent transcriptional repression domain in RVR, characterized critical amino acids within the silencing region and provide evidence for the physiological role of RVR during myogenesis [5].

Biological context of Nr1d2

• We show that RVR recognizes this hormone response element with a specificity similar to that of the orphan receptor ROR alpha 2 [6].
• Northern blot analysis reveals that two RVR mRNA species are expressed during mouse embryogenesis and widely expressed in adult tissues [6].
• This new orphan receptor, cloned from a mouse brain cDNA library, is closely related to the rat Rev-ErbA alpha gene product (97% and 68% identity in the DNA- and ligand-binding domains, respectively) and referred to as RVR [6].
• Studies with in vitro translated RVR protein show that it binds the DNA sequence ATAACTAGGTCA, a hormone response element composed of a 6-base pair AT-rich sequence preceding a single nuclear receptor recognition half-site core motif PuGGTCA [6].
• However, cotransfection studies indicate that RVR does not activate transcription when this hormone response element is linked to a reporter gene but rather acts as a potent competitive repressor of ROR alpha function [6].

Anatomical context of Nr1d2

• Although RVR is expressed in many adult tissues, including skeletal muscle, and during embryogenesis, its physiological function in differentiation and mammalian development remains unknown [5].
• In C2C12 myogenic cells, RVR mRNA was detected in proliferating myoblasts and was suppressed when the cells were induced to differentiate into post-mitotic, multinucleated myotubes by serum withdrawal [5].
• beta-Gal enzyme activity driven by the HSV LAT promoter does not correspond to beta-gal RNA levels in mouse trigeminal ganglia [7].
• beta 1D is a recently identified isoform of the beta 1 integrin subunit selectively expressed in skeletal and cardiac muscles [8].
• beta 3-Adrenergic agonist induces a functionally active uncoupling protein in fat and slow-twitch muscle fibers [9].

Associations of Nr1d2 with chemical compounds

• Transcriptional repression by the orphan steroid receptor RVR/Rev-erb beta is dependent on the signature motif and helix 5 in the E region: functional evidence for a biological role of RVR in myogenesis [5].
• "beta CATECHIN", a preparation of natural vitamins and phytosubstances, has been designed as an "universal antioxidant' drink [10].

Other interactions of Nr1d2

• We have cloned Rev-erb beta, a novel isoform of the Rev-erb alpha orphan nuclear receptor [11].

Analytical, diagnostic and therapeutic context of Nr1d2

• However, titration of this 15 bp duplex with ReDBD, the DNA binding domain of Rev-erb beta, showed large shifts of imino protons and 31P signals, suggesting major conformational changes [12].

References