Transcriptome analysis of different brain areas in Hcrt gene and Hcrt cell ablated mice. 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. Overall design: 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).