The phenotypic impact of CSF1R enhancer fms-intronic regulatory element (FIRE) deletion in NSG mice

Zoë A. Galvin

Document Type

Article

Publication Date

2025

Keywords

JMG

Abstract

The study of neuroimmunology suffers from a lack of effective and translational model organisms due to intrinsic differences of biology between mouse models and human disease. This limitation spurred the need for a model organism which houses and expresses human neuroimmunological cells for effective study. The Shultz lab created the NSG-Csf1r FIRE KO/KO Mouse (NSG-FIRE KO/KO) in response to this need. This mouse model does not support several populations of resident macrophage cells, notably including microglia, which results in a complex phenotype characterized by a lowered lifespan and multiple observed phenotypic abnormalities. This project completed a series of clinical scorings on several NSG-FIRE KO/KO related genotypes and concluded that NSG-FIRE KO/KO mice expresses many observed neurological changes compared with NSG-FIRE WT/WT mice. Interestingly, most of these deficits were not present in NSG-FIRE KO/KO mice co-expressing the human SGM3 triple transgene despite continued microglia absence, which points to an impact on non-microglia myeloid cell populations in NSG-FIRE KO/KO mice. In vitro studies on murine bone marrow from FIRE KO/KO mice showed reduced levels of macrophage proteins related to macrophage activation and recruitment of T-cells. These data support the development of this model as human microglia xenograft recipients and use in understanding the role of FIRE in macrophage populations.

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

COinS