» Articles » PMID: 34090462

Humanized Mice for Infectious and Neurodegenerative Disorders

Abstract

Humanized mice model human disease and as such are used commonly for research studies of infectious, degenerative and cancer disorders. Recent models also reflect hematopoiesis, natural immunity, neurobiology, and molecular pathways that influence disease pathobiology. A spectrum of immunodeficient mouse strains permit long-lived human progenitor cell engraftments. The presence of both innate and adaptive immunity enables high levels of human hematolymphoid reconstitution with cell susceptibility to a broad range of microbial infections. These mice also facilitate investigations of human pathobiology, natural disease processes and therapeutic efficacy in a broad spectrum of human disorders. However, a bridge between humans and mice requires a complete understanding of pathogen dose, co-morbidities, disease progression, environment, and genetics which can be mirrored in these mice. These must be considered for understanding of microbial susceptibility, prevention, and disease progression. With known common limitations for access to human tissues, evaluation of metabolic and physiological changes and limitations in large animal numbers, studies in mice prove important in planning human clinical trials. To these ends, this review serves to outline how humanized mice can be used in viral and pharmacologic research emphasizing both current and future studies of viral and neurodegenerative diseases. In all, humanized mouse provides cost-effective, high throughput studies of infection or degeneration in natural pathogen host cells, and the ability to test transmission and eradication of disease.

Citing Articles

The ABC transporter A7 modulates neuroinflammation via NLRP3 inflammasome in Alzheimer's disease mice.

Santos-Garcia I, Bascunana P, Brackhan M, Villa M, Eiriz I, Bruning T Alzheimers Res Ther. 2025; 17(1):30.

PMID: 39871385 PMC: 11773842. DOI: 10.1186/s13195-025-01673-2.


In situ analysis of neuronal injury and neuroinflammation during HIV-1 infection.

Honeycutt J, Wahl A, Files J, League A, Yadav-Samudrala B, Garcia J Retrovirology. 2024; 21(1):11.

PMID: 38945996 PMC: 11215835. DOI: 10.1186/s12977-024-00644-z.


Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation.

Buck L, Xie Q, Willis M, Side C, Giacometti L, Gaskill P Commun Biol. 2024; 7(1):387.

PMID: 38553542 PMC: 10980811. DOI: 10.1038/s42003-024-06079-8.


Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection.

Mu W, Patankar V, Kitchen S, Zhen A Viruses. 2024; 16(2).

PMID: 38399994 PMC: 10893210. DOI: 10.3390/v16020219.


Delimiting MOGAD as a disease entity using translational imaging.

Oertel F, Hastermann M, Paul F Front Neurol. 2024; 14:1216477.

PMID: 38333186 PMC: 10851159. DOI: 10.3389/fneur.2023.1216477.


References
1.
Tycko J, Myer V, Hsu P . Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity. Mol Cell. 2016; 63(3):355-70. PMC: 4976696. DOI: 10.1016/j.molcel.2016.07.004. View

2.
Boska M, Dash P, Knibbe J, Epstein A, Akhter S, Fields N . Associations between brain microstructures, metabolites, and cognitive deficits during chronic HIV-1 infection of humanized mice. Mol Neurodegener. 2014; 9:58. PMC: 4297430. DOI: 10.1186/1750-1326-9-58. View

3.
Gorantla S, Makarov E, Finke-Dwyer J, Castanedo A, Holguin A, Gebhart C . Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. Am J Pathol. 2010; 177(6):2938-49. PMC: 2993281. DOI: 10.2353/ajpath.2010.100536. View

4.
Fields J, Spencer B, Swinton M, Qvale E, Marquine M, Alexeeva A . Alterations in brain TREM2 and Amyloid-β levels are associated with neurocognitive impairment in HIV-infected persons on antiretroviral therapy. J Neurochem. 2018; 147(6):784-802. PMC: 6310632. DOI: 10.1111/jnc.14582. View

5.
Cai L, Fisher A, Huang H, Xie Z . CRISPR-mediated genome editing and human diseases. Genes Dis. 2018; 3(4):244-251. PMC: 6150104. DOI: 10.1016/j.gendis.2016.07.003. View