This technology is a transgenic mouse line with Vps26a heterozygous knockout that can be used to study the role of the retromer core in Alzheimer’s disease.
Unmet Need: Mouse model for studying retromer dedicated to endosomal recycling
Pathogenic disruptions in retromer-mediated endosomal trafficking are observed in Alzheimer’s disease (AD). Disruption in the retromer pathway impacts different brain regions with various severity, and the underlying mechanisms of the disease remain unknown. Although a target for studying AD pathology, there are currently no dedicated mouse models to selectively disrupt this pathway.
The Technology: Vps26a transgenic mice for studying retromer complex in neurological disorders
This technology describes a transgenic mouse line with heterozygous knockout of Vps26a. Western blot analysis confirmed a reduction in Vps26 protein level, but the mice survive into adulthood with no developmental abnormalities. Hippocampal-dependent memory function deficits have been observed in this mouse line with memory-related behavior tasks. This mouse line can also be used to compare with the knockout of other retromer-related genes.
Applications:
- Mouse model for studying neurodegenerative diseases
- Mouse model for studying prenatal and developmental disorders
- Research tool for analysis of retromer function in different brain regions
- Selection of therapeutic drugs targeting retromer complex
Advantages:
- Specific targeting of Vps26a
- Heterozygous line for partial loss-of-function
- Comparable to other transgenic mouse lines
Lead Inventor:
Scott A. Small, M.D.
Related Publications:
Muhammad A, Flores I, Zhang H, Yu R, Staniszewski A, Planel E, Herman M, Ho L, Kreber R, Honig LS, Ganetzky B, Duff K, Arancio O, Small SA. “Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Aβ accumulation” Proc Natl Acad Sci U S A. 2008 May 20; 105(20): 7327-7332.
Simoes S, Guo J, Buitrago L, Qureshi YH, Feng X, Kothiya M, Cortes E, Patel V, Kannan S, Kim Y‑H, Chang K‑T, Hussaini SA, Moreno H, Di Paolo G, Andersen OM, Small SA. “Alzheimer’s vulnerable brain region relies on a distinct retromer core dedicated to endosomal recycling” Cell Rep. 2021 Dec 28; 37(13): 110182.
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