A transcriptional enhancer that directs telencephalon-specific transgene expression in mouse brain

Telencephalin (TLCN, intercellular adhesion molecule-5 [ICAM-5]) is a cell adhesion molecule belonging to the immunoglobulin superfamily, which plays important roles in dendritic morphogenesis and synaptic plasticity. The expression of TLCN is restricted to neurons in the most rostral brain segment, telencephalon. Here, we examined a transcriptional regulatory mechanism underlying the telencephalon-specific expression of TLCN. TLCN gene is located in the ICAM gene cluster containing ICAM-1, ICAM-4, and TLCN (ICAM-5) within 30 kb on the mouse chromosome 9. The nucleotide sequence of the 5'-flanking region of mouse TLCN gene is highly homologous to that of human and dog orthologs, suggesting the presence of important regulatory elements for its transcription. To determine the telencephalon-specific enhancer region, we generated several lines of transgenic mice that harbor transgenes consisting of different length of the 5'-flanking region of mouse TLCN gene (3.9, 1.5, 1.1, and 0.2 kb) fused to humanized renilla green fluorescent protein cDNA as a fluorescent reporter. Consequently, we identified a crucial region between 1.1 and 0.2 kb upstream of the transcription start site that directs the telencephalon-specific expression. This enhancer was applied to the Cre/loxP-mediated conditional expression system to generate several transgenic lines with different patterns of recombination in the telencephalon and will be further used as a powerful tool for genetic manipulation in the telencephalic neurons.