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

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 beta-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.

• Authors: Helen C Freeman, Alison Hugill, Neil T Dear, Frances M Ashcroft, Roger D Cox
• Journal: Diabetes (Diabetes) Vol. 55 Issue 7 Pg. 2153-6 (Jul 2006) ISSN: 0012-1797 [Print] United States
• PMID: 16804088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Insulin
• NADP Transhydrogenases

Topics

• Animals
• Blood Glucose (metabolism)
• Chromosomes, Artificial, Bacterial
• Exons
• Glucose Intolerance (enzymology, genetics)
• Insulin (blood)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Transgenic
• NADP Transhydrogenases (deficiency, genetics)
• Quantitative Trait Loci
• Sequence Deletion