A 5' UTR Mutation Contributes to Down-Regulation of in the Berlin Fat Mouse.

The Bardet-Biedl Syndrome 7 () gene was identified as the most likely candidate gene causing juvenile obesity in the Berlin Fat Mouse Inbred (BFMI) line. expression is significantly lower in the brain, adipose tissue, and liver of BFMI mice compared to lean C57BL/6NCrl (B6N) mice. A DNA sequence comparison between BFMI and B6N revealed 16 sequence variants in the promoter region. Here, we tested if these mutations contribute to the observed differential expression of . In a cell-based dual-luciferase assay, we compared the effects of the BFMI and the B6N haplotypes of different regions of the promotor on the reporter gene expression. A single-nucleotide polymorphism (SNP) was identified causing a significant reduction in the reporter gene expression. This SNP (rs29947545) is located in the 5' UTR of at Chr3:36.613.350. The SNP is not unique to BFMI mice but also occurs in several other mouse strains, where the BFMI allele is not associated with lower transcript amounts. Thus, we suggest a compensatory mutation in the other mouse strains that keeps expression at the normal level. This compensatory mechanism is missing in BFMI mice and the cell lines tested.