Poster Presentation 39th Annual Lorne Genome Conference 2018

Mechanisms of regulation of the transcription factor Single-Minded 1 in obesity (#149)

Alexis G Gerassimou 1 , Adrienne E Sullivan 1 , David C Bersten 1 , Murray L Whitelaw 1
  1. School of Biological Sciences, University of Adelaide, Adelaide, SOUTH AUSTRALIA, Australia

The basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor Single Minded 1 (SIM1) has essential roles in the development and function of hypothalamic cell lineages. Non-synonymous point mutants of SIM1 have established SIM1 deficiency to be a monogenic cause of obesity in humans, while haploinsufficiency studies in mice revealed increased weight gain due to hyperphagia and increased linear growth. Several studies indicate that SIM1 plays an important role in the appetite controlling Leptin-Melanocortin signalling pathway in the hypothalamus, however the target genes of SIM1 and its up- and downstream regulatory pathways have yet to be defined. To further our understanding of the role of SIM1 in appetite control, we have generated a transgenic mouse model with GFP under the control of the Sim1 promoter composite with a weakly functioning mutant of SIM1. This mouse model, in combination with cell based assays, will be used to identify novel target genes and investigate mechanisms of regulation of SIM1.