Disruption of Igfbp1 fails to rescue the phenotype of Sirt1-/- mice.
Sirtuin 1 (SIRT1) is an NAD-dependent histone deacetylase (HDAC) whose activity is thought to forestall the onset of a variety of age-related diseases. Mice carrying null mutations of the Sirt1 gene suffer high rates of neonatal lethality and those that survive are sterile, growth retarded, lean and their livers express high levels of insulin-like growth factor binding protein-1 (IGFBP1). IGFBP1 binds and regulates the bioavailability of Igfs. Interestingly, Igfbp1 transgenic mice largely phenocopy Sirt1-/- mice, suggesting the possibility that the over-expression of IGFBP1 in Sirt1-/- mice might be responsible for many of their phenotypes. We interbred Sirt1 heterozygote mice to Igfbp1-deficient mice to test the hypothesis that the disruption of one or both alleles of Igfbp1 would rescue the phenotype of Sirt1-/- mice. We report that mono- or bi-allelic disruption of the Igfbp1 gene had no effect on the embryonic and neonatal lethality of Sirt1-/- mice. However, we show that mice lacking at least one allele of both Sirt1 and Igfbp1 genes have a much higher incidence of malocclusion.
Boily
Gino
G
Center for Cancer Therapeutics, Ottawa Hospital Research Institute, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6.
He
Xiao Hong
XH
Jardine
Karen
K
McBurney
Michael W
MW
D000818:Animals; D003433:Crosses, Genetic; D005838:Genotype; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000502:physiology*; D008310:Malocclusion / Q000209:etiology* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D056564:Sirtuin 1 / Q000502:physiology*
D018970:Insulin-Like Growth Factor Binding Protein 1; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1