Characterization of the 5′-sequence of the mouse fatty acid amide hydrolase

Abstract

Fatty acid amide hydrolase (FAAH) is critical for degradation of several important fatty acid amides including anandamide, an endocannabinoid, as well as oleamide, a sleep-inducing factor. These compounds play roles in diverse physiological processes ranging from memory and learning to the regulation of blood pressure. The mechanisms that regulate FAAH expression have not been characterized. A 5′-region of the mouse FAAH with promoter activity was isolated from 1.8 kbp of genomic sequence. Characterization of +1 of transcription of FAAH by RNA ligase mediated-rapid amplification of cDNA ends showed that FAAH mRNA is transcribed from multiple transcription start sites lacking a TATA-box element. Functional analysis of the FAAH upstream sequence fused to a luciferase reporter gene revealed a FAAH-promoter construct with tissue specific activity. A 674-bp FAAH-promoter construct was active in N18TG2 (N18) neuroblastoma cells and C6 glioma cells, lines that have endogenous FAAH activity. The same 674-bp FAAH-promoter construct was not active in C2C12 or L6 myogenic cells, two lines that do not have FAAH activity.