Have you ever had an experimental design deviate from expectations? Well, this episode is for you. Associate Editor Dr. Keith Brunt (Dalhousie University) interviews Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) about her recently published article by Hu et al., along with content expert Dr. Joshua Man ( Tufts Medical Center), to discuss how unexpected results and negative findings can, in and of themselves, lead to new discoveries. Kassiri and co-authors used a Cre/lox system to study the role of disintegrin and metalloproteinase-17 (Adam17) in smooth muscle cells (SMC) in a mouse model of atherosclerosis. LDL-deficient mice that consumed a high fat diet had normal skin. However, mice with floxed alleles of Adam17 driven by Sm22alpha developed severe skin lesions. The loss of gene function and Sm22alpha expression was apparent in keratinocytes. Adam17 deletion by a different SMC driver, Myh11-Cre, did not result in skin lesions in the same atherosclerosis model. Staying true to the expression that experience is what you get when you don’t get what you want, Hu et al. published their results in the hopes of helping other labs and animal care & use committees avoid similar pitfalls. What are the potential ramifications for cardiovascular researchers, keratinocyte biologists, and dermatologists? Listen and find out.

 

Mei Hu, Sho Hiroyasu, David J. Granville, Zamaneh Kassiri Implications of Sm22alpha-Cre expression in keratinocytes and unanticipated inflammatory skin lesion in a model of atherosclerosis  Am J Physiol Heart Circ Physiol, published August 31, 2022. DOI: 10.1152/ajpheart.00325.2022