Transcriptome analysis of different brain areas in Hcrt gene and Hcrt cell ablated mice

Hypocretin (HCRT) and melanin concentrating hormone (MCH) are brain neuropeptides regulating a wide range of functions including sleep and metabolism. Loss of function of HCRT causes the sleep disorder narcolepsy. We found that loss of HCRT neurons in Hcrt-ataxin-3 mice results in a specific 50% decrease in another orexigenic neuropeptide QRFP that might explain the metabolic syndrome in narcolepsy. To identify cell type-specific regulators of HCRT cells, we used two commonly used mouse models of narcolepsy with cataplexy: Hcrt gene knockout (Hcrtko/ko) mice and Hcrt-ataxin-3 mice in which HCRT cells are ablated by the expression of ataxin-3 gene. We hypothesized that comparing the brain transcriptome of these mice and their controls might identify transcriptional changes due both to a lack of Hcrt gene and HCRT neurons altogether (as in narcolepsy).