Skip to main content
Open Access Publications from the University of California

UC Irvine

UC Irvine Previously Published Works bannerUC Irvine

Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.

  • Author(s): 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;
  • Shahnawaz, Mohammad;
  • Matheos, Dina P;
  • Ma, Xinyi;
  • Da Cunha, Celia;
  • Walls, Ken C;
  • Ager, Rahasson R;
  • Soto, Claudio;
  • Gutierrez, Antonia;
  • Moreno-Gonzalez, Ines;
  • Mortazavi, Ali;
  • Tenner, Andrea J;
  • MacGregor, Grant R;
  • Wood, Marcelo;
  • Green, Kim N;
  • LaFerla, Frank M
  • et al.

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View