The authors show that the hepatic expression of the hepatic specific humanised APP gene (HSHA) in 6, 12, 18 and 24 month mice that leads to the synthesis of human amyloid beta that results in accelerated lipid inclusion bodies, parenchymal extravasation of apo B proteins, marked neovascular inflammation, exaggerated cerebral abundance of amyloid beta, chronic neurodegeneration, brain atrophy in regions associated with cognitive performance and impaired hippocampal dependent learning. The insertion of the transgene HSHA may control of the hepatic gene expression and regulation of transcription of various genes. This HSHAtransgenic mouse model and its effects on other hepatic genes and their products may be important to human gene therapy for the treatment of human diseases. The HSHA transgenic mouse model may need to provide a liver heat map for gene expression from these mice. The relevance of the HSHA transgenic model may be relevant to various other transgenic mouse models and their relevance to global chronic disease, metabolic dysfunction and Alzheimer’s disease.
RELEVANT REFERENCES:
1. Lam V, Takechi R, Hackett MJ, Francis R, Bynevelt M, Celliers LM, et al. (2021) Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like phenotype. PLoS Biol 19(9): e3001358.
2. COMBAT AD HSHA Journal Club Presentation, 24092021. Please see attached.
3. Bartholomeus C.M. (Benno) Haarman, Rixt F. Riemersma-Van der Lek, Willem A. Nolen, R. Mendes, Hemmo A. Drexhage, Huibert Burger. Feature-expression heat maps – A new visual method to explore complex associations between two variable sets. Journal of Biomedical Informatics, Volume 53, 2015, Pages 156-161.
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