1.
J Inherit Metab Dis. 2007 Nov;30(6):888-95. Epub 2007 Nov 19.

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

Author information

1
Division of Medical Genetics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Rangos Research Building, Room 2113, 3460 Fifth Ave., Pittsburgh, PA 15213, USA.

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-alpha 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.

PMID:
18008182
DOI:
10.1007/s10545-007-0776-7
[Indexed for MEDLINE]
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