Toolbox: Orexin-B-SAP – Advanced Targeting Systems

ATS is pleased to re-release a product and kit specific for the Orexin 2 receptor (OX2R). The Orexin 1 and Orexin 2 receptors are found in the perifornical area/latero-posterior hypothalamus, and projections from this area cover much of the brain. These receptors have been implicated in various neurophysiological and neuropsychological disorders such as narcolepsy, insomnia, drug addiction, anxiety, and migraine headaches. The Orexin-B-SAP conjugate consists of the rat/mouse-specific orexin-B peptide conjugated to Saporin. Orexin-B binds to OX2R with approximately 5X greater affinity than to OX1R (Fig. 2).

Orexin-B-SAP (Cat. #IT-20) is highly specific for cells that express OX2R. Instead of spending precious time and money producing an OX2R knockout animal, you can use Orexin-B-SAP to specifically eliminate cells that express OX2R (Fig. 1). Orexin-B-SAP also allows you to study the behavioral effects before and after treatment and subsequent elimination of OX2R expressing cells. The specificity and efficacy of Orexin-B-SAP has recently been reported in the published work of Schwartz et al.

See also Toolbox: Orexin Receptor Antibody Conjugates.

KnockoutMouse — Fig. 1: Targeted toxins offer the ability to develop “knockouts” through cell surface-based targeting that has several advantages over the gene-based approach. The “knockout” has a slight but important difference: instead of knocking out a particular protein from a set of cells (or even the whole animal), you eliminate a particular cell type. And this happens at your convenience: you inject the animal, put it back in its cage and then usually four days later, behavioral differences begin to show. These usually become permanent after a week or so.

Fig. 2: The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1R and OX2R. There are two orexin peptides: Orexin A and Orexin B. These peptides bind to both receptors, however, Orexin B shows a >5-fold selectivity for OX2R . Orexin A is equipotent at both receptors.

Schwartz MD, Nguyen AT, Warrier DR, Palmerston JB, Thomas AM, Morairty SR, Neylan TC, Kilduff TS. (2016) Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin Antagonist-Mediated REM Sleep. eNeuro 3(2) PMID: 27022631.