GSE132715
Mouse Homolog of a Human TP53 Germline Mutation Reveals a Lipolytic Activity of p53
The physiological effects of the many germline mutations of TP53, encoding the tumor suppressor protein p53, are poorly understood.  Here, we report generating a p53 R178C knockin mouse modeling the human TP53 R181C mutation that is notable for its prevalence and prior molecular characterization.  Consistent with its weak cancer penetrance in humans, homozygous p53178C/C mice showed a modest increase in tumorigenesis but, surprisingly, were lean with decreased body fat content.  They displayed evidence of increased lipolysis and upregulation of fatty acid metabolism in their inguinal white adipose tissue (iWAT).  Gene expression and chromatin immunoprecipitation sequencing (ChIP-Seq) analyses showed that the mutant p53 bound and transactivated Beta-3-Adrenergic Receptor (ADRB3), a gene that is known to promote lipolysis and is associated with obesity.  The current study reveals that a germline mutation of p53 can affect fat metabolism which can impact cancer development. Overall design: RNA-seq data of white adipose tissue obtained from wild-type p53, homozygous p53 R178C knockin mutant, and homozygous p53 knockout mice.  p53 ChIP-seq data of adipocytes derived from the stromal vascular fraction of adipose tissue.