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

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33 Scopus citations

Abstract

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
Volume30
Issue number6
DOIs
StatePublished - Nov 2007

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Hager, E. J., Tse, H. M., Piganelli, J. D., Gupta, M., Baetscher, M., Tse, T. E., Pappu, A. S., Steiner, R. D., Hoffmann, G. F., & Gibson, K. M. (2007). Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome. Journal of inherited metabolic disease, 30(6), 888-895. https://doi.org/10.1007/s10545-007-0776-7