A mutation in NFkB interacting protein 1 results in cardiomyopathy and abnormal skin development in wa3 mice

Bruce J. Herron, Cherie Rao, Shanming Liu, Lisa Laprade, James A. Richardson, Emily Oliveri, Chris Semsarian, Sarah E. Millar, Lisa Stubbs, David R. Beier

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

We have identified waved 3 (wa3), a novel recessive mutation that causes abnormalities of the heart and skin. The cardiac defect results in a severe and rapidly progressive dilated cardiomyopathy. We identified the gene mutated in these mice, which we call NFkB interacting protein1 (Nkip1), using positional cloning. Nkip1 is expressed in skin, heart and vascular endothelium and shares homology with a small family of proteins that play a role in the regulation of transcription factors. A C-terminal fragment of this protein was previously identified as the ReIA associated inhibitor (RAI). We show that the full-length protein is larger than previously described, and we confirm that it interacts with NFkB in vivo. Expression analysis of genes known to be regulated by NFkB revealed that Intercellular adhesion molecule 1 (Icam1) expression is consistently elevated in mutant mice. This result suggests that wa3 mutant mice represent a potentially important model for the analysis of the role of inflammatory processes in heart disease.

Original languageEnglish (US)
Pages (from-to)667-677
Number of pages11
JournalHuman molecular genetics
Volume14
Issue number5
DOIs
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Herron, B. J., Rao, C., Liu, S., Laprade, L., Richardson, J. A., Oliveri, E., Semsarian, C., Millar, S. E., Stubbs, L., & Beier, D. R. (2005). A mutation in NFkB interacting protein 1 results in cardiomyopathy and abnormal skin development in wa3 mice. Human molecular genetics, 14(5), 667-677. https://doi.org/10.1093/hmg/ddi063