Mouse Model of Alzheimer’s Disease Gets UC San Diego License

Ana de Barros, PhD avatar

by Ana de Barros, PhD |

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Tarrytown, New York-based PsychoGenics has announced its Line-41 mouse model of Alzheimer’s disease (AD) has obtained a license from the University of California, San Diego. This experimental model expresses human APP with the London (V717I) and Swedish (K670N/M671L) mutations under the murine-Thy-1 promoter control.

PsychoGenics is a leader in providing preclinical central nervous system services. The company has pioneered the translation of rodent behavioral responses into robust, high content phenotyping, and its drug discovery platforms — PhenoCube, NeuroCube  and SmartCube — have led to shared-risk partnerships with leading pharmaceutical companies like Roche and Sunovion, resulting in the discovery of several novel compounds, now in clinical trials and advanced preclinical development.

In this new model, mice show early onset and progressive plaque disposition in their cerebral cortex and hippocampus as early as three to four months. A number of other hallmarks of human Alzheimer’s disease summarized in the Line-41 mice include:

  • Dystrophic neurites that contain hyperphosphorylated tau protein in the microenvironment of mature plaques and cognitive impairment linked to the appearance of neuro-inflammation, characterized by increased micro-glia activation and astroglioses starting at six months, with a progressive worsening as the amyloid load increases.

The Line-41 mouse model was developed by Profs. Edward Rockenstein and  Eliezer Masliah at UCSD and overexpresses human APP with the London mutation and the Swedish double mutation under the neuron-specific Thy1 promoter control.

“Using our extensive array of behavioral tests, including our Cube technology platforms and our full range of services in electrophysiology, biochemistry, neurochemistry, and quantitative immunohistochemistry, we expect to be able to identify an even earlier Alzheimer’s disease-associated phenotype in Line-41 which will enable companies not only to assess treatment strategies but also to explore prevention and early intervention approaches,” said Emer Leahy, Ph.D., president and CEO of PsychoGenics, in a press release.

“We are very excited to add this mouse model to our portfolio of Alzheimer’s models, which include both mice (the Tg2576 and APP/PS1 from the University of South Florida) and rat (the McGill-R-Thy1-APP) models of amyloidosis, and a Tauopathy mouse model, the rTg4510, from the Mayo Clinic,” Leahy said. “The Line-41 model displays key features of human Alzheimer’s disease, and together with some of our other models, offers a valuable tool to assess anti-neuroinflammatory and A-beta lowering strategies as treatments for Alzheimer’s disease.”