Splenic extramedullary hemopoiesis caused by a dysfunctional mutation in the NF-κB-inducing kinase gene

Biochem Biophys Res Commun. 2011 Nov 4;414(4):773-8. doi: 10.1016/j.bbrc.2011.10.001. Epub 2011 Oct 7.

Abstract

NF-κB-inducing kinase (NIK) plays critical roles in the development of lymph nodes and Peyer's patches, and microarchitecture of the thymus and spleen via NF-κB activation. Alymphoplasia (aly/aly) mice have a point mutation in the NIK gene that causes a defect in the activation of an NF-κB member RelB. Here, we developed a novel method to determine the aly mutation by genetic typing using PCR. This method facilitated the easy establishment of a congeneic aly/aly mouse line. Indeed, we generated a mouse line with aly mutation on a BALB/cA background (BALB/cA-aly/aly). BALB/cA-aly/aly mice showed significant splenomegaly with extramedullary hemopoiesis, which was not significant in aly/aly mice on a C57BL/6 background. Interestingly, the splenomegaly and extramedullary hemopoiesis caused by the aly mutation was gender-dependent. These data together with previous reports on extramedullary hemopoiesis in RelB-deficient mice suggest that NIK-RelB signaling may be involved in the suppression of extramedullary hemopoiesis in adult mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Hematopoiesis, Extramedullary / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics*
  • Spleen / physiology
  • Splenomegaly / genetics
  • Transcription Factor RelB / genetics
  • Transcription Factor RelB / metabolism*

Substances

  • Relb protein, mouse
  • Transcription Factor RelB
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase