Nur77 variants solely comprising the amino-terminal domain activate hypoxia-inducible factor-1α and affect bone marrow homeostasis in mice and humans.

ABSTRACT: Gene targeting via homologous recombination can occasionally result in incomplete disruption of the targeted gene. Here, we show that a widely used Nur77-deficient transgenic mouse model expresses a truncated protein encoding for part of the N-terminal domain of nuclear receptor Nur77. This truncated Nur77 protein is absent in a newly developed Nur77-deficient mouse strain generated using Cre-Lox recombination. Comparison of these two mouse strains using immunohistochemistry, flow cytometry, and colony-forming assays shows that homologous recombination-derived Nur77-deficient mice, but not WT or Cre-Lox-derived Nur77-deficient mice, suffer from liver immune cell infiltrates, loss of splenic architecture, and increased numbers of bone marrow hematopoietic stem cells and splenic colony-formi

SUBMITTER: Koenis DS 

PROVIDER: S-EPMC6166732 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature