title: Functional and morphological alterations in compound transgenic mice overexpressing Cu/Zn superoxide dismutase and amyloid precursor protein [correction].
abstract: Down's syndrome (DS), the phenotypic manifestation of trisomy 21, involves overexpression of chromosome 21-encoded genes. The gene for amyloid precursor protein (APP), known to be involved in AD pathology, resides on chromosome 21 along with the gene for Cu/Zn superoxide dismutase (SOD1), a key enzyme in the metabolism of oxygen free radicals. We investigated the consequences of a combined increase in APP and SOD1, in a double-transgenic (tg)-APP-SOD1 mouse. These mice expressed severe impairment in learning, working and long-term memory. Expression of long-term potentiation in hippocampal slices was impaired in both tg-SOD and tg-APP-SOD mice, but not in tg-APP mice, indicating that increased APP by itself did not affect in vitro synaptic plasticity. In tg-APP-SOD mice, membrane-bound high molecular weight APP species accumulated while APP cleavage products did not increase and levels of secreted APP were unchanged. Severe morphological damage, including lipofuscin accumulation and mitochondria abnormalities, were found in aged tg-APP-SOD but not in the other mice. Thus, a combined elevation of the two chromosome 21 genes in tg-APP-SOD mice induced age-dependent alterations in morphological and behavioural functions.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Catherine
authors.initials: C
authors.lastname: Harris-Cerruti
authors.forename: Ariel
authors.initials: A
authors.lastname: Kamsler
authors.forename: Batia
authors.initials: B
authors.lastname: Kaplan
authors.forename: Bruce
authors.initials: B
authors.lastname: Lamb
authors.forename: Menahem
authors.initials: M
authors.lastname: Segal
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D013482:Superoxide Dismutase