Identification of Molecular Mechanisms Acting at the jObes1 Locus in the Berlin Fat Mouse With Effect on Juvenile Fat Deposition

The aim of the project is the elucidation of the mechanism causing obesity in the Berlin Fat Mouse (BFMI). This mouse harbors a spontaneous mutation on mouse chromosome 3 (jObes1 locus) accounting for the high fat deposition particularly during puberty. Fine mapping, complementation tests and gene expression studies have identified the Bardet Biedl Syndrome 7 (Bbs7) gene as most likely candidate gene. Bbs7 contributes to the formation of cilia and mutations in this gene may cause the Bardet-Biedl-Syndrome in humans. Like humans, BFMI mice are overweight, have degraded retinae and alterations in the brain. The standard protein sequence of Bbs7 has been excluded as cause for the defects in BFMI mice. Sequence data and expression profiles provide evidence for regulatory acting sequence variants leading to alternative Bbs7 expression patterns. In addition, interactions between mutated DNA regions could affect the expression of Bbs7 as well as neighboring genes. To identify the mechanisms underlying the malfunction of different tissues, we intend to perform genomic sequencing, transcription studies, tests to estimate effects of mutations and studies on the genome architecture.