The orphan nuclear transcription factor encoded by the Nr4a1 gene is involved in neuron development & maintenance, myofiber size and muscle mass, wound healing, progesterone receptor-mediated permeability responses in uterine embryo implantation, angiogenesis, anti-inflammation, and glucose homeostasis. These NGFI-B or Nur77 mutant mice carry a targeted mutation in which a PGK-NEO cassette disrupts exon 2. Mice homozygous for the allele and on a congenic FVB/N background are viable and fertile. The Donating Investigator reports that the congenic FVB/N background does not alter the phenotype observed in B6;129 mixed and congenic C57BL/6 Nr4a1tm1Jmi mutant mice. On the C57BL/6 background, knock-out mice have greatly diminished angiogenic response to VEGF-A, histamine or serotonin induction, and are more susceptible to diet-induced obesity and insulin resistance.
Of note, although the original analysis of this allele revealed no detectable transcript of any type from this gene in the thymus, findings by Koenis, 2018 (PMID 30111591) indicate the presence of a transcript capable of producing a truncated N-terminal domain (NTD) peptide that can stabilize and activate HIF1A (hypoxia inducible factor 1, alpha subunit). Neither the transcriptional nor the translational start of the gene are disrupted.
