An approach to promoting survival of human microglia in humanized mouse models of Alzheimer's Disease


Lauren Baptiste

Document Type


Publication Date

Summer 2023



JAX Location

In: Student Reports, Summer 2023, The Jackson Laboratory


Alzheimer’s Disease (AD) is a leading cause of dementia, characterized by the development of amyloid beta (Aβ) plaques and hyperactivation of microglia. In the presence of Aβ, hyperactivated microglia become dysfunctional and damage the surrounding neurons. To better understand the role of human microglia during AD pathogenesis, our aim is to create a humanized mouse model for the study of human microglia in vivo. This preliminary study will employ three strategies ideal for a model of human microglia in AD: introducing amyloid plaques, engrafting human microglia, and eliminating mouse microglia. First, for the development of plaques, APP/PS1 transgenic mice, expressing proteins which are human AD risk factors, will be investigated. Second, to promote survival and successful engraftment of human microglia, we utilized human interleukin 34 (hIL34) transgenic mice. IL34 is a ligand of colony stimulating factor 1 receptor (CSF1R), a receptor expressed in microglia whose binding is necessary for cell survival. Third, we eliminated the confounding variable of mouse microglia through a genetic knockout of fms-intronic regulatory element (FIRE). This intronic enhancer promotes transcription of the gene encoding for CSF1R, and without this enhancer, mouse microglia do not express CSF1R and do not develop. Our findings confirm the feasibility of each of these strategies alone, and in the future, we hope to combine these strategies to create a comprehensive humanized mouse model of AD.

Please contact the Joan Staats Library for information regarding this document.