Deletion of nicotinamide nucleotide transhydrogenase: a new quantitive trait locus accounting for glucose intolerance in C57BL/6J mice.
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.
Freeman
Helen C
HC
Medical Research Council, Mammalian Genetics Unit, Harwell, Oxfordshire, UK.
Hugill
Alison
A
Dear
Neil T
NT
Ashcroft
Frances M
FM
Cox
Roger D
RD
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial; D005091:Exons; D018149:Glucose Intolerance / Q000201:enzymology / Q000235:genetics*; D007328:Insulin / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009250:NADP Transhydrogenases / Q000172:deficiency / Q000235:genetics*; D040641:Quantitative Trait Loci; D017384:Sequence Deletion
D001786:Blood Glucose; D007328:Insulin; D009250:NADP Transhydrogenases