Disease relevance of Hcrtr2

• Blockade of the OX2-OX2R interaction with an OX2R mAb exacerbated the disease model experimental allergic encephalomyelitis [1].

Psychiatry related information on Hcrtr2

• Exon skipping mutations of the Hypocretin/Orexin-receptor-2 (Hcrtr2) gene were identified as the cause of narcolepsy in Dobermans and Labradors [2].
• In contrast, OX2R(-/-) mice are only mildly affected with cataplexy-like attacks of REM sleep, whereas orexin(-/-) mice are severely affected [3].
• Both OX2R(-/-) and orexin(-/-) mice are similarly affected with behaviorally abnormal attacks of non-REM sleep ("sleep attacks") and show similar degrees of disrupted wakefulness [3].

High impact information on Hcrtr2

• Pervanandate treatment of macrophages showed that OX2R could be phosphorylated on tyrosine residues [1].
• OX2 and its receptor are both cell surface glycoproteins containing two immunoglobulin-like domains and interact with a dissociation constant of 2.5 microM and koff 0.8 s(-1), typical of many leukocyte protein membrane interactions [1].
• The OX2 membrane glycoprotein (CD200) is expressed on a broad range of tissues including lymphoid cells, neurons, and endothelium [1].
• While normal regulation of wake/non-REM sleep transitions depends critically upon OX2R activation, the profound dysregulation of REM sleep control unique to the narcolepsy-cataplexy syndrome emerges from loss of signaling through both OX2R-dependent and OX2R-independent pathways [3].
• This alteration results in a single amino acid substitution (E54K) in the N-terminal region of the Hcrtr2 receptor and autosomal recessive transmission in a Dachshund family [2].

Biological context of Hcrtr2

• Results indicate a truncated Hcrtr2 protein, an absence of proper membrane localization, and undetectable binding and signal transduction for exon-skipping mutated constructs [2].

Anatomical context of Hcrtr2

• In this experiment, we measured the expressions of these peptides as well as of their receptors (OX1-R and OX2-R, Y1 and Y5) in the hypothalamus of obese hyperphagic and lean Zucker rats by real-time RT-PCR using the TaqMan apparatus [4].
• PURPOSE: OX2 is a member of the immunoglobulin superfamily expressed on a broad range of tissues including neurons of the central and peripheral nervous systems, thymocytes, and endothelium [5].
• During experimental autoimmune uveoretinitis (EAU), expression of both OX2 and OX2R was noted on infiltrating leukocytes [5].
• The recently identified OX2 receptor (OX2R) is restricted to the surfaces of myeloid lineage cells, including microglia [5].
• RESULTS: OX2 was expressed on retinal vascular endothelium and glial fibrillary acidic protein (GFAP)-negative neurons in retina and optic nerve and on a subpopulation of CD45(+) perivascular and juxtavascular cells [5].

Associations of Hcrtr2 with chemical compounds

• Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function [1].

References