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The Widely Used Ucp1-Cre Transgene Elicits Complex Developmental and Metabolic Phenotypes

Halurkar et al., Nature Communications. 2025.

https://pubmed.ncbi.nlm.nih.gov/39824816

Bacterial artificial chromosome technology is instrumental to mouse transgenics, including in studies of highly thermogenic brown adipose tissue and energy-storing white adipose tissue. Researchers discovered that male and female Ucp1-CreEvdr transgenic mice, which are commonly used to study fat tissue, may have unintended effects on metabolism and development. Findings revealed that these mice show changes in both brown and white fat function and disruptions in gene activity, suggesting broader physiological impacts than previously thought. This study emphasizes the need for careful validation of genetic tools in research to ensure accurate results, highlighting the potential concerns in using the Ucp1-CreEvdr model in metabolic and developmental studies. Supported by ORIP (R21OD034470, R21OD031907) NCATS, NIDCR, and NIDDK.

Synthetic Protein Circuits for Programmable Control of Mammalian Cell Death

Xia et al., Cell. 2024.

https://pubmed.ncbi.nlm.nih.gov/38657604/

Natural cell-death pathways have been shown to eliminate harmful cells and shape immunity. Researchers used synthetic protein-level cell-death circuits, collectively termed “synpoptosis” circuits, to proteolytically regulate engineered executioner proteins and mammalian cell death. They show that the circuits direct cell death modes, respond to combinations of protease inputs, and selectively eliminate target cells. This work provides a foundation for programmable control of mammalian cell death. Future studies could focus on programmable control of cell death in various contexts, including cancer, senescence, fibrosis, autoimmunity, and infection. Supported by ORIP (F30OD036190) and NIBIB.

Gigapixel Imaging With a Novel Multi-Camera Array Microscope

Thomson et al., eLife. 2022.

https://www.doi.org/10.7554/eLife.74988

The dynamics of living organisms are organized across many spatial scales. The investigators created assembled a scalable multi-camera array microscope (MCAM) that enables comprehensive high-resolution, large field-of-view recording from multiple spatial scales simultaneously, ranging from structures that approach the cellular scale to large-group behavioral dynamics. By collecting data from up to 96 cameras, they computationally generated gigapixel-scale images and movies with a field of view over hundreds of square centimeters at an optical resolution of 18 µm. This system allows the team to observe the behavior and fine anatomical features of numerous freely moving model organisms on multiple spatial scales (e.g., larval zebrafish, fruit flies, slime mold). Overall, by removing the bottlenecks imposed by single-camera image acquisition systems, the MCAM provides a powerful platform for investigating detailed biological features and behavioral processes of small model organisms. Supported by ORIP (R44OD024879), NIEHS, NCI, and NIBIB.