title: 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.affiliation: Medical Research Council, Mammalian Genetics Unit, Harwell, Oxfordshire, UK.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Freeman
authors.forename: Alison
authors.initials: A
authors.lastname: Hugill
authors.forename: Neil T
authors.initials: NT
authors.lastname: Dear
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cox
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009250:NADP Transhydrogenases