Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity.

Abstract	Dihydronicotinamide riboside (NRH):quinone oxidoreductase 2 (NQO2) is a flavoenzyme that catalyzes the reductive metabolism of quinones. To examine the in vivo role of NQO2, NQO2-null (NQO2-/-) mice were generated using targeted gene disruption. Mice lacking NQO2 gene expression showed no detectable developmental abnormalities and were indistinguishable from wild-type (NQO2+/+) mice. However, NQO2-null mice exhibited myeloid hyperplasia of the bone marrow and increased neutrophils, basophils, eosinophils, and platelets in the peripheral blood. Decreased apoptosis of bone marrow cells and circulating granulocytes contributed to myeloid hyperplasia and hyperactivity of bone marrow in NQO2-null mice. The hematological changes in NQO2-/- mice were specifically associated with loss of the NQO2 gene because histological analysis of various tissues including spleen, thymus, blood cultures, and urine analysis demonstrated no sign of infection. NQO2-null mice also demonstrated decreased toxicity when exposed to menadione or menadione with NRH. These results establish a role for NQO2 in protection against myelogenous hyperplasia and in metabolic activation of menadione, leading to hepatic toxicity. The NQO2-null mice are a model for NQO2 deficiency in humans and can be used to determine the role of this enzyme in sensitivities to toxicity and carcinogenesis.
Authors	Delwin J Long 2nd, Karim Iskander, Amos Gaikwad, Meral Arin, Dennis R Roop, Richard Knox, Roberto Barrios, Anil K Jaiswal
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 48 Pg. 46131-9 (Nov 29 2002) ISSN: 0021-9258 [Print] United States
PMID	12351651 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	DNA Primers Vitamin K 3 NRH - quinone oxidoreductase2 Quinone Reductases
Topics	Animals Base Sequence Bone Marrow (drug effects, enzymology, pathology) Cloning, Molecular DNA Primers Fertility (genetics) Flow Cytometry Hyperplasia Liver (drug effects, pathology) Mice Mice, Knockout Polymerase Chain Reaction Quinone Reductases (genetics, metabolism) Vitamin K 3 (toxicity)

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