title: Overexpression of liver-type phosphofructokinase (PFKL) in transgenic-PFKL mice: implication for gene dosage in trisomy 21.
abstract: The human liver-type subunit of the key glycolytic enzyme, phosphofructokinase (PFKL), is encoded by a gene residing on chromosome 21. This chromosome, when triplicated, causes the phenotypic expression of Down's syndrome (trisomy 21). Increased phosphofructokinase activity, a result of gene dosage, is commonly found in erythrocytes and fibroblasts from Down's syndrome patients. We describe the construction of transgenic mice overexpressing PFKL for use as a well-defined model system, in which the effects of PFKL overexpression in various tissues, and throughout development, can be studied. Mice transgenic for a murine PFKL 'gene cDNA' hybrid construct were found to overexpress PFKL in a tissue-specific manner resembling that of the endogenous enzyme. Although unchanged in adult brain, PFK specific activity was found to have been almost doubled in brains of embryonic transgenic-PFKL mice, suggesting that the extra copies of the PFKL gene are expressed during the developmental period. This pattern of overexpression of PFKL in brains of transgenic-PFKL mice suggests that gene-dosage effects may be temporally separated from some of their consequences, adding an additional layer of complexity to the analysis of gene dosage in trisomy 21.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute, Rehovot, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Elson
authors.forename: D
authors.initials: D
authors.lastname: Levanon
authors.forename: Y
authors.initials: Y
authors.lastname: Weiss
authors.forename: Y
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002891:Chromosomes, Human, Pair 21; D017931:DNA Primers; D004314:Down Syndrome / Q000201:enzymology* / Q000235:genetics*; D005091:Exons; D015870:Gene Expression; D006801:Humans; D007438:Introns; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000254:growth & development; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D010732:Phosphofructokinase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012016:Reference Values; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D015345:Oligonucleotide Probes; D010732:Phosphofructokinase-1