Physical activity and body weight maintenance: What is the molecular link?
Endokrinologie, Diabetologie, Metabolismus
Zusammenfassung der Projektergebnisse
The aim of the project was to investigate the role of the hypothalamic transcription factor BSX (brain-specific homeobox factor) in physical activity. We were especially interested if BSX function is linked to a known neuronal network or if BSX defines its own. We addressed this question employing the cre-lox technology to create different mouse lines that carry a KO of BSX in defined neuronal cell populations. Although we were able to generate several conditional KO mice, we could not resemble the phenotype of a complete KO by using AgRP- ,Leptin- or HDC-Cre-mouse lines. Further, we established a novel automated phenotyping platform that enabled us high resolution recording of metabolic parameters. Using the BSX knockout model in this system, we could demonstrate that the loss of activity caused by a monogenetic alteration can lead to higher fat accumulation. We also wanted to characterize the function of DNA elements that regulate BSX expression. Based on bioinformatics analysis we could identify highly conserved sequences that are potential cis-regulatory elements. To validate the functions of those potential elements, we employed Crispr/Cas9 based transgenesis to delete these elements. Unfortunately, we could not observe any detectable changes in BSX expression in single element-deleted transgenic mice, implying that regulation of BSX expression is complex and that the loss of single element can be compensated by other elements. Nevertheless, we were able to define the genomic region covering all cis-regulatory elements for controlling BSX expression.
