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, Anuradha Pappu, R. D. Steiner, G. F. Hoffmann, K. Michael Gibson

Research output: Contribution to journalArticle

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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) 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

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mevalonate kinase
Mevalonate Kinase Deficiency
Alleles
Dolichol
Immunoglobulin D
Mevalonic Acid
Ubiquinone
Liver

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Endocrinology

Cite this

Hager, E. J., Tse, H. M., Piganelli, J. D., Gupta, M., Baetscher, M., Tse, T. E., ... 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

Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome. / Hager, E. J.; Tse, H. M.; Piganelli, J. D.; Gupta, M.; Baetscher, M.; Tse, T. E.; Pappu, Anuradha; Steiner, R. D.; Hoffmann, G. F.; Gibson, K. Michael.

In: Journal of Inherited Metabolic Disease, Vol. 30, No. 6, 11.2007, p. 888-895.

Research output: Contribution to journalArticle

Hager, EJ, Tse, HM, Piganelli, JD, Gupta, M, Baetscher, M, Tse, TE, Pappu, A, Steiner, RD, Hoffmann, GF & Gibson, KM 2007, 'Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome', Journal of Inherited Metabolic Disease, vol. 30, no. 6, pp. 888-895. https://doi.org/10.1007/s10545-007-0776-7
Hager, E. J. ; Tse, H. M. ; Piganelli, J. D. ; Gupta, M. ; Baetscher, M. ; Tse, T. E. ; Pappu, Anuradha ; Steiner, R. D. ; Hoffmann, G. F. ; Gibson, K. Michael. / Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome. In: Journal of Inherited Metabolic Disease. 2007 ; Vol. 30, No. 6. pp. 888-895.
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