Int J Biol Sci 2018; 14(5):542-548. doi:10.7150/ijbs.24303 This issue

Short Research Communication

Generation of Smurf2 Conditional Knockout Mice

Yi Tang1, Liu-Ya Tang1, Xuan Xu1, Cuiling Li2, Chuxia Deng2,3, Ying E. Zhang1✉

1. Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
2. Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
3. Present address: Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, China.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Tang Y, Tang LY, Xu X, Li C, Deng C, Zhang YE. Generation of Smurf2 Conditional Knockout Mice. Int J Biol Sci 2018; 14(5):542-548. doi:10.7150/ijbs.24303. Available from

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Graphic abstract

Smad ubiquitin regulatory factor 2 (Smurf2) is a HECT domain-containing E3 ubiquitin ligase. Together with its closely related homolog Smurf1, Smurf2 was initially recognized as a negative regulator of transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling, but subsequent studies have expanded its function to regulate many different signaling pathways and play important roles in genomic stability, cell polarity, tissue homeostasis and carcinogenesis. Mice with conventional knockout of Smurf1 or Smurf2 alleles are viable, but conventional Smurf1 and Smurf2 double knockout mice were early embryonic lethal. In order to study the physiological function of Smurfs during late stage of embryonic development or in adult animals, we generated Smurf2flox/flox mice carrying a targeted mutation for conditional Smurf2 gene inactivation. We demonstrated that Cre-mediated recombination using Alb-Cre, a Cre line expressed in hepatocyte, results in specific deletion of the gene in liver tissue. We also showed that Cre-mediated recombination in mouse embryonic fibroblasts (MEFs) with Smurf2flox/flox genotype resulted in generation of Smurf2 knockout MEFs, and Smurf2 deficiency affects multiple signaling pathways. Therefore, this animal model will be useful to study the distinct roles of Smurf2 in different tissues at different ages.

Keywords: Smurf2, Liver, Mice, LoxP, Knockout