Background and Aims The genetic components and mechanisms causing obesity still are poorly understood.
Using the Berlin Fat Mouse Inbred (BFMI) line in crossbred experiments, we identified
the jObes1 locus on chromosome 3 explaining around 40 % of the obese phenotype. Through
complementation tests, Bbs7 was identified as the most likely candidate gene in the
jObes1 region. Sequencing showed a 1578 bp deletion in intron 8 of Bbs7 which removes
a CTCF binding site.
Material and Methods To investigate the role of this deletion, we generated B6N mice carrying a deletion
similar to BFMI mice using the CRISPR / Cas9 system. In total 6 founders with deletions
were obtained. The exact deletion start and end points were determined, and complementation
tests were performed. Therefore, mice carrying a CRISPR / Cas9 deletion were crossed
with mice carrying BFMI or B6N alleles. Parental BFMI haplotypes were compared to
other mouse strains from the Mouse Genome Project database.
Results One of the founder families used for complementation tests indicates that the CRISPR / Cas9
deletion, which includes the CTCF binding site, is capable of partially complementing
the BFMI deletion. Haplotype analysis revealed no unique SNP in the Bbs7 gene in BFMI
compared to many other mouse strains.
Conclusion Preliminary data suggest a role of the CTCF binding site in the obese phenotype.
This is underpinned by the lack of unique SNPs compared to other mouse lines in this
region.
