1. The widely used Ucp1-Cre Evdr transgene elicits complex developmental and metabolic phenotypes.
- Author
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Halurkar MS, Inoue O, Mukherjee R, Paese CLB, Duszynski M, Brugmann SA, Lim HW, and Sanchez-Gurmaches J
- Abstract
Bacterial artificial chromosome transgenic models, including most Cre-recombinases , enable potent interrogation of gene function in vivo but require rigorous validation as limitations emerge. Due to its high relevance to metabolic studies, we performed comprehensive analysis of the Ucp1-Cre
Evdr line which is widely used for brown fat research. Hemizygotes exhibited major brown and white fat transcriptomic dysregulation, indicating potential altered tissue function. Ucp1-CreEvdr homozygotes also show high mortality, growth defects, and craniofacial abnormalities. Mapping the transgene insertion site revealed insertion in chromosome 1 accompanied by large genomic alterations disrupting several genes expressed in a range of tissues. Notably, Ucp1-CreEvdr transgene retains an extra Ucp1 gene copy that may be highly expressed under high thermogenic burden. Our multi-faceted analysis highlights a complex phenotype arising from the presence of the Ucp1-CreEvdr transgene independently of the intended genetic manipulations. Overall, comprehensive validation of transgenic mice is imperative to maximize discovery while mitigating unexpected, off-target effects., Competing Interests: Conflict of interest: The authors declare no conflict of interest.- Published
- 2023
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