title: Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in humans.
abstract: The rise in fructose consumption, and its correlation with symptoms of metabolic syndrome (MBS), has highlighted the need for a better understanding of fructose metabolism. To that end, valid rodent models reflecting the same metabolism as in humans, both biochemically and physiologically, are critical. A key to understanding any type of metabolism comes from study of disease states that affect such metabolism. A serious defect of fructose metabolism is the autosomal recessive condition called hereditary fructose intolerance (HFI), caused by mutations in the human aldolase B gene (Aldob). Those afflicted with HFI experience liver and kidney dysfunction after fructose consumption, which can lead to death, particularly during infancy. With very low levels of fructose exposure, HFI patients develop non-alcoholic fatty acid liver disease and fibrosis, sharing liver pathologies also seen in MBS. A major step toward establishing that fructose metabolism in mice mimics that of humans is reported by investigating the consequences of targeting the mouse aldolase-B gene (Aldo2) for deletion in mice (Aldo2(-/-)). The Aldo2(-/-) homozygous mice show similar pathology following exposure to fructose as humans with HFI such as failure to thrive, liver dysfunction, and potential morbidity. Establishing that this mouse reflects the symptoms of HFI in humans is critical for comparison of rodent studies to the human condition, where this food source is increasing, and increasingly controversial. This animal should provide a valuable resource for answering remaining questions about fructose metabolism in HFI, as well as help investigate the biochemical mechanisms leading to liver pathologies seen in MBS from high fructose diets.
authors: Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, 5 Cummington Mall, Boston, MA 02215, USA. Electronic address: oppelts@bu.edu.
authors: Sarah A
authors: SA
authors: Oppelt
authors: Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, 5 Cummington Mall, Boston, MA 02215, USA. Electronic address: emsennott@gmail.com.
authors: Erin M
authors: EM
authors: Sennott
authors: Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, 5 Cummington Mall, Boston, MA 02215, USA; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02215, USA. Electronic address: tolan@bu.edu.
authors: Dean R
authors: DR
authors: Tolan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005632:Fructose / Q000008:administration & dosage / Q000378:metabolism; D005633:Fructose Intolerance / Q000235:genetics; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D006801:Humans; D007668:Kidney; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D018345:Mice, Knockout; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: D005632:Fructose; D005634:Fructose-Bisphosphate Aldolase
keywords: Hepatic; Inborn errors in metabolism; Liver failure; Obesity; Steatosis; Sugar metabolism