Contains a disruption of the Pparα (peroxisome proliferator activated receptor alpha(α)) gene in the ligand-binding coding region
Pparα, a member of the nuclear steroid/hormone receptor superfamily, is involved in fatty acid metabolism and transport and mediates the induction of peroxisome proliferation
No profound hepatomegaly, peroxisomal proliferation and induction of fatty acid oxidation enzymes in response to classical peroxisome proliferators
Higher serum HDL cholesterol and apoA-I concentrations than wild type controls
β-oxidation of the long-chain fatty acid, palmitic acid, is lower in mutant mice, demonstrating altered mitochondrial fatty acid metabolism
β-oxidation of very long chain fatty acids is not altered
Useful in studies of lipid and glucose homeostasis, to study fatty acid metabolism and as a potential model for inborn errors of metabolism
Genetic Background: C57BL/6 Background
The Pparα targeted mutation model was developed by Susana S.T. Lee and colleagues in the laboratory of Frank Gonzalez at the National Cancer Institute. The model was created by targeting the Pparα gene in 129S4 derived J1 ES cells and injecting the targeted cells into C57BL/6N blastocysts. Resultant chimeras were backcrossed to C57BL/6N for eleven generations (N11). Taconic received stock in 2001. Mice were backcrossed to C57BL/6N for embryo transfer derivation (N12). The colony is maintained by incrossing homozygous mice.
Wild type for Nnt mutation; carries Pde6brd1 mutation
Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ. (1995) Targeted disruption of the a isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol, 15(5):3012-22.