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Gene Review

Hcrtr2  -  hypocretin (orexin) receptor 2

Mus musculus

Synonyms: Hypocretin receptor type 2, Mox2r, OX2R, OX2r, Orexin receptor type 2, ...
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Disease relevance of Hcrtr2


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].


  1. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Wright, G.J., Puklavec, M.J., Willis, A.C., Hoek, R.M., Sedgwick, J.D., Brown, M.H., Barclay, A.N. Immunity (2000) [Pubmed]
  2. Identification and functional analysis of mutations in the hypocretin (orexin) genes of narcoleptic canines. Hungs, M., Fan, J., Lin, L., Lin, X., Maki, R.A., Mignot, E. Genome Res. (2001) [Pubmed]
  3. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Willie, J.T., Chemelli, R.M., Sinton, C.M., Tokita, S., Williams, S.C., Kisanuki, Y.Y., Marcus, J.N., Lee, C., Elmquist, J.K., Kohlmeier, K.A., Leonard, C.S., Richardson, J.A., Hammer, R.E., Yanagisawa, M. Neuron (2003) [Pubmed]
  4. Opposite regulation of hypothalamic orexin and neuropeptide Y receptors and peptide expressions in obese Zucker rats. Beck, B., Richy, S., Dimitrov, T., Stricker-Krongrad, A. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  5. Distribution of OX2 antigen and OX2 receptor within retina. Dick, A.D., Broderick, C., Forrester, J.V., Wright, G.J. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
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