| Autor: |
Baglietto-Vargas, David, Forner, Stefania, Cai, Lena, Martini, Alessandra C., Trujillo-Estrada, Laura, Swarup, Vivek, Nguyen, Marie Minh Thu, Do Huynh, Kelly, Javonillo, Dominic I., Tran, Kristine Minh, Phan, Jimmy, Jiang, Shan, Kramár, Enikö A., Nuñez-Diaz, Cristina, Balderrama-Gutierrez, Gabriela, Garcia, Franklin, Childs, Jessica, Rodriguez-Ortiz, Carlos J., Garcia-Leon, Juan Antonio, Kitazawa, Masashi |
| Předmět: |
|
| Zdroj: |
Nature Communications; 4/23/2021, Vol. 12 Issue 1, p1-16, 16p |
| Abstrakt: |
The majority of Alzheimer's disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules. Most instances of Alzheimer's disease (AD) are sporadic or not associated with a particular mutation. Here, the authors develop knock-in mice that express wildtype human Aβ under control of the mouse App locus, which may have potential for modelling some aspects of sporadic late onset AD. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Full text from SpringerLink