A Case of Mistaken Identity

tion, may mediate or contribute to these findings. colleagues (1999) is to characterize the truncated pro-any, between hypocretins and HLA-DQB1*0602 in hu-19, 248–257. mans. HLA class II molecules, such as HLA-DQB1*0602, are expressed in the nervous system and bind peptides; whether or not a particular peptide is bound depends on which antigen is expressed. If HLA-DQB1*0602 binds hypocretins, its presence in the nervous system could alter hypocretin activity and, in combination with aberrant receptor function, lead to narcolepsy. Assessment of Hcrtr2 density in the brains of canine and human We are fascinated by mermaids, centaurs, and other narcoleptics may also be fruitful. mythical chimeras at least in part because they chal-Finally, a mouse model of narcolepsy based on muta-lenge our notion that identity is exclusive. Within the tions or deletion of the Hcrtr2 gene would greatly in-nervous system, a neuron's identity is defined by its crease the availability and ease of use of this model for function. For example, motor neurons (MNs) relay infor-neuroscientists interested in sleep and sleep disorders. mation between the central nervous system (CNS) and In the August 20 issue of Cell, Chemelli and colleagues muscle, whereas interneurons relay information solely (1999) describe just such a model. They produced a within the CNS. But are these features mutually exclu-prepro-orexin (prepro-hypocretin) knockout mouse that sive, or, like a mermaid or centaur, could a neuron ex-is characterized by abnormalities of REM sleep and peri-press features of both MN and interneuron identities? ods of behavioral arrest that may represent cataplexy Apparently so, since this is precisely the phenotype of or sudden sleep episodes. While it remains to be deter-MNs in mice lacking function of the Hb9 homeobox mined whether this model duplicates all major aspects gene, as described in two papers in this issue of Neuron of human narcolepsy, including excessive sleepiness, (Arber et al., 1999; Thaler et al., 1999). the electrophysiological similarities are striking. Contin-Despite the clear functional differences between MNs ued study of these mice should lead to significant ad-and interneurons, evidence from chicks, mice, and ze-vances in understanding the control and regulation of brafish suggest that these cells share an early develop-sleep and wakefulness. Selected Reading located interneurons and raise the question of what directs a cell toward one or the other identity.