BAd-CRISPR Accelerates Adipose Tissue Research

Studying how adipose tissue functions in the body is critical for understanding obesity and other issues, yet structural differences in fat cells and their distribution throughout the body make doing so challenging. This could be changing as a paper published recently in the Journal of Biological Chemistry describes a new CRISPR-based approach that could speed discoveries in brown adipose tissue biology.

“The biggest challenge in terms of adipose research to date has been that if you want to study a gene’s function, you have to commit a considerable amount of time, resources, and money into developing a transgenic mouse,” explained Steven Romanelli, first author of the paper.

The team’s new approach, called brown adipocyte CRISPR (BAd-CRISPR), can rapidly interrogate the function of one or multiple genes. “What we’ve been able to do is take that whole process and distill it into anywhere from two weeks to a month to generate a transgenic mouse, reducing the cost to less than $2,000. Not only does it reduce time and cost, it democratizes the research so that any lab that is familiar with molecular biology techniques can adopt this method and do it themselves,” Romanelli added.

They were also able to use this method to delete multiple genes simultaneously, a fact that could help researchers better understand important molecular pathways.

Using their adeno-associated virus CRISPR-Cas9 components, they were able to knockout the UCP1 gene that defines brown adipose and enables it to generate heat, in adult mice. They observed that the knockout mice were able to adapt to the loss of the gene and maintain their body temperature in cold conditions, hinting at other pathways involved in temperature homeostasis.