Analysis Tools|
Allele Symbol Allele Name Allele ID |
Mvkem4Mijr endonuclease-mediated mutation 4, Michael J Rogers MGI:8246880 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice have approximately 50% of normal mevalonate kinase activity in liver compared to wild-type mice
• however, mice show no defect in prenylation of small GTPases
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show increased mevalonic acid levels in plasma and bone marrow cell extracts and a buildup of unprenylated GTPases in peripheral blood mononuclear cells, splenocytes and bone marrow
• mutant recipients of wild-type bone marrow retain elevated plasma mevalonic acid levels, however wild-type hosts receiving mutant bone marrow show low plasma mevalonic acid levels indicating that nonhematopoietic tissues appear to be the source of plasma mevalonic acid in mutants
• mice kept in a heated chamber for 18 hours which raised core body temperature by 2.5 degrees Celsius exhibit a further elevation of circulating mevalonic acid compared to wild-type mice which show no effect of plasma mevalonic acid levels in response to temperature and plasma mevalonic acid returns to baseline levels upon 48 hours recovery at standard housing temperature
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• mice exhibit 9% and 5% of normal mevalonate kinase activity in liver and bone marrow, respectively
• mice kept in a heated chamber for 18 hours which raised core body temperature by 2.5 degrees Celsius exhibit a 3-fold lower mevalonate kinase activity (barely detectable) in spleen compared to unheated mice or wild-type controls
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| N |
• under steady-state conditions, mice do not show any differences in the frequencies of B cells, T cells, dendritic cells, neutrophils, or monocytes in peripheral blood, spleen, or bone marrow and the level of inflammatory cytokines and chemokines in serum is barely detectable, and serum IgD is undetectable, indicating lack of inflammation under basal/unstimulated conditions
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• mice treated with a bisphosphonate drug, alendronate, to inhibit protein prenylation show unchanged frequencies of immune cell populations in the peritoneal cavity unlike controls which show increased infiltration of immune cells indicating a lack of alendronate-induced inflammation
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• mice treated with LPS show an increase in the levels of several inflammatory serum cytokines and chemokines (IL-1beta, IL-18, IL-6, G-CSF, IL-12, CCL2, CCL3, and CCL5) compared to heterozygous Mvkem1Mijr mice and in several of these factors (G-CSF, IL-6, IL-12,a nd CCL2) in the peritoneal fluid
• however, circulating levels of IFN-gamma and TNF-alpha are not different in LPS-treated mice
• administration of a single dose of the NLRP3 inhibitor MCC950 1 hour prior to LPS challenge completely abolished the increase in IL-18 and reduces IL-1beta release to near baseline circulating levels and slightly reduces serum IL-6, CCL2, and CCL5, but not G-CSF, CCL3, or IL-12
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hyperimmunoglobulinemia D periodic fever syndrome | DOID:0081450 |
OMIM:260920 |
J:371663 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 09/30/2025 MGI 6.24 |
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