Deletion of nicotinamide nucleotide transhydrogenase: A new quantitive trait locus accounting for glucose intolerance in C57BL/6J mice

Helen C. Freeman, Alison Hugill, Neil T. Dear, Frances M. Ashcroft, Roger D. Cox

Research output: Contribution to journalArticlepeer-review

192 Citations (Scopus)


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 inframe 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.

Original languageEnglish
Pages (from-to)2153-2156
Number of pages4
Issue number7
Publication statusPublished - Jul 2006


  • BAC, bacterial artificial chromosome
  • IPGTT, intraperitoneal glucose tolerance test
  • Nnt, nicotinamide nucleotide transhydrogenase
  • QTLs, quantitative trait loci

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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