A 5’ UTR Mutation Contributes To Down-Regulation Of Bbs7 In The Berlin Fat Mouse

The Bardet Biedl syndrome 7 ( Bbs7 ) gene was identified as the most likely candidate gene causing juvenile obesity in the Berlin Fat Mouse Inbred (BFMI) line. Bbs7 is significantly lower expressed in brain, adipose tissue, and liver of BFMI mice compared to lean C57BL/6NCrl (B6N) mice. DNA sequence comparison between BFMI and B6N revealed 16 sequence variants in the Bbs7 promoter region. Here, we tested if these mutations contribute to the observed differential expression of Bbs7 .In a cell-based dual luciferase assay we compared the effects of the BFMI and the B6N haplotypes of different regions of the Bbs7 promotor on the reporter gene expression. A single SNP was identified causing a significant reduction in the reporter gene expression. This SNP (rs29947545) is located in the 5’ UTR of Bbs7 at Chr3:36.613.350. The SNP is not unique to BFMI mice, but occurs also in several other mouse lines, where the BFMI allele is not associated with lower Bbs7 transcript amounts. As such, a second factor alongside the SNP rs29947545 or interacting with the SNP location is likely required to cause the reduction of Bbs7 expression which leads to the obese phenotype in BFMI mice.