| First Author | Shukkur EA | Year | 2006 |
| Journal | Hum Mol Genet | Volume | 15 |
| Issue | 18 | Pages | 2752-62 |
| PubMed ID | 16891409 | Mgi Jnum | J:114926 |
| Mgi Id | MGI:3690407 | Doi | 10.1093/hmg/ddl211 |
| Citation | Shukkur EA, et al. (2006) Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome. Hum Mol Genet 15(18):2752-62 |
| abstractText | Trisomy 21 or Down syndrome (DS) is the most common genetic birth defect associated with mental retardation. The over-expression of genes on chromosome 21, including SOD1 (Cu/Zn superoxide dismutase) and APP (amyloid-beta precursor protein) is believed to underlie the increased oxidative stress and neurodegeneration commonly described in DS. However, a segmental trisomy 16 mouse model for DS, Ts1Cje, has a subset of triplicated human chromosome 21 gene orthologs that exclude APP and SOD1. Here, we report that Ts1Cje brain shows decreases of mitochondrial membrane potential and ATP production, increases of reactive oxygen species, hyperphosphorylation of tau without NFT formation, increase of GSK3beta and JNK/SAPK activities and unaltered AbetaPP metabolism. Our findings suggest that genes on the trisomic Ts1Cje segment other than APP and SOD1 can cause oxidative stress, mitochondrial dysfunction and hyperphosphorylation of tau, all of which may play critical roles in the pathogenesis of mental retardation in DS. |
