Generation and Characterization of a Humanized Lung Xenograft Mouse Model for Studying Henipavirus Pathogenesis

Gustavo Valbuena; Barry Rockx; Olivier Escaffre

doi:10.1007/978-1-0716-3283-3_14

Generation and Characterization of a Humanized Lung Xenograft Mouse Model for Studying Henipavirus Pathogenesis

Methods Mol Biol. 2023:2682:191-204. doi: 10.1007/978-1-0716-3283-3_14.

Authors

Gustavo Valbuena¹, Barry Rockx², Olivier Escaffre³

Affiliations

¹ UC Berkeley-UCSF Joint Medical Program, Berkeley, CA, USA.
² Wageningen Bioveterinary Institute, Lelystad and Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
³ Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. olescaff@utmb.edu.

PMID: 37610583
DOI: 10.1007/978-1-0716-3283-3_14

Abstract

The development of humanized mouse models has recently opened new avenues in the field of infectious diseases. These models allow research on many human viruses that were once difficult to study, because finding suitable animal models of infection can be challenging, cost prohibitive, and often do not entirely recapitulate all parameters of the disease. Here, we describe the procedure of human immune system reconstitution (humanization) of NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG) mice by the bone marrow, liver, and thymus (BLT) reconstitution method as well as the process of human lung engraftment. We then describe how to infect these human lung grafts with the paramyxovirus Nipah virus (NiV) that can cause lethal respiratory disease in humans, and for which there is only limited understanding of pathogenesis to acute lung injury.

Keywords: BLT reconstitution; Henipavirus; Human lung xenograft; Humanized mouse model; Immune response; NSG mice.

MeSH terms

Animals
Disease Models, Animal
Henipavirus*
Heterografts
Humans
Lung
Mice
Mice, Inbred NOD
Mice, SCID