Hcrtr2-KO Mouse

Hcrtr2, also known as orexin receptor 2 (OX2R), is a G-protein-coupled receptor. It binds to the endogenous neuropeptides hypocretin/orexin, which are crucial for regulating the sleep-wake cycle. Hcrtr2 is strongly linked to sleep-wake control and is part of the endogenous sleep-wake regulatory circuitry [1].

In mice, inactivation of Hcrtr2 specifically in dopaminergic neurons led to hyperarousal, as indicated by increased theta electroencephalographic (EEG) activity in wakefulness and rapid-eye-movement sleep (REMS). These mice also showed enhanced cognition but impaired inhibitory control, suggesting a role of Hcrtr2 in attentional processes and executive functions relevant to disorders like narcolepsy, attention-deficit/hyperactivity disorder, and Parkinson's disease [2].

In conclusion, Hcrtr2 is essential for maintaining normal sleep-wake regulation. Gene-knockout or conditional-knockout mouse models have revealed its role in hyperarousal and cognitive-behavioral functions, which are relevant to multiple neurological and psychiatric disorders. Understanding Hcrtr2 through these research models provides insights into the mechanisms underlying these diseases and may offer potential therapeutic targets.