Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome

E. J. Hager, H. M. Tse, J. D. Piganelli, M. Gupta, M. Baetscher, T. E. Tse, A. S. Pappu, R. D. Steiner, G. F. Hoffmann, K. Michael Gibson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


In the current study our objective was to develop a murine model of human hyper-IgD syndrome (HIDS) and severe mevalonic aciduria (MA), autoinflammatory disorders associated with mevalonate kinase deficiency (MKD). Deletion of one Mvk allele (Mvk+/-) yielded viable mice with significantly reduced liver Mvk enzyme activity; multiple matings failed to produce Mvk-/- mice. Cholesterol levels in tissues and blood, and isoprene end-products (ubiquinone, dolichol) in tissues were normal in Mvk+/- mice; conversely, mevalonate concentrations were increased in spleen, heart, and kidney yet normal in brain and liver. While the trend was for higher IgA levels in Mvk+/- sera, IgD levels were significantly increased (9-12-fold) in comparison to Mvk+/+ littermates, in both young (<15 weeks) and older (>15 weeks) mice. Mvk+/- animals manifested increased serum TNF-α as compared to wild-type littermates, but due to wide variation in levels between individual Mvk+/- mice the difference in means was not statistically significant. Mvk+/- mice represent the first animal model of HIDS, and should prove useful for examining pathophysiology associated with this disorder.

Original languageEnglish (US)
Pages (from-to)888-895
Number of pages8
JournalJournal of inherited metabolic disease
Issue number6
StatePublished - Nov 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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