| First Author | Halurkar MS | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 770 |
| PubMed ID | 39824816 | Mgi Jnum | J:363052 |
| Mgi Id | MGI:7858307 | Doi | 10.1038/s41467-024-54763-4 |
| Citation | Halurkar MS, et al. (2025) The widely used Ucp1-Cre transgene elicits complex developmental and metabolic phenotypes. Nat Commun 16(1):770 |
| abstractText | 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 perform comprehensive analysis of the Ucp1-Cre(Evdr) line which is widely used for brown fat research. Hemizygotes exhibit major brown and white fat transcriptomic dysregulation, indicating potential altered tissue function. Ucp1-Cre(Evdr) homozygotes also show high mortality, tissue specific growth defects, and craniofacial abnormalities. Mapping the transgene insertion site reveals insertion in chromosome 1 accompanied by large genomic alterations disrupting several genes expressed in a range of tissues. Notably, Ucp1-Cre(Evdr) 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-Cre(Evdr) transgene independently of intended genetic manipulations. Overall, comprehensive validation of transgenic mice is imperative to maximize discovery while mitigating unexpected, off-target effects. |
