Deletion of Nicotinamide Nucleotide Transhydrogenase
A New Quantitive Trait Locus Accounting for Glucose Intolerance in C57BL/6J Mice
- 1Mammalian Genetics Unit, Medical Research Council, Harwell, Oxfordshire, U.K
- 2University Laboratory of Physiology, Parks Road, Oxford, U.K
- Address correspondence and reprint requests to Professor Roger D. Cox, Medical Research Council, Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 0RD, U.K. E-mail: r.cox{at}har.mrc.ac.uk
Abstract
The C57BL/6J mouse displays glucose intolerance and reduced insulin secretion. The genetic locus underlying this phenotype was mapped to nicotinamide nucleotide transhydrogenase (Nnt) on mouse chromosome 13, a nuclear-encoded mitochondrial protein involved in β-cell mitochondrial metabolism. C57BL/6J mice have a naturally occurring in-frame five-exon deletion in Nnt that removes exons 7–11. This results in a complete absence of Nnt protein in these mice. We show that transgenic expression of the entire Nnt gene in C57BL/6J mice rescues their impaired insulin secretion and glucose-intolerant phenotype. This study provides direct evidence that Nnt deficiency results in defective insulin secretion and inappropriate glucose homeostasis in male C57BL/6J mice.
- BAC, bacterial artificial chromosome
- IPGTT, intraperitoneal glucose tolerance test
- Nnt, nicotinamide nucleotide transhydrogenase
- QTLs, quantitative trait loci
Footnotes
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Additional information for this article can be found in an online appendix at http://diabetes.diabetes.org.
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted April 18, 2006.
- Received March 17, 2006.
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