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Updated: Apr 4, 2026
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Influence of age, irradiation and humanization on NSG mouse phenotypes
Jaclyn S Knibbe-Hollinger1, Natasha R Fields1, Tammy R Chaudoin2
1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Abstract:
Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization.
Insights
Humanized mice models show age and irradiation impact health, affecting blood and behavior. This data helps researchers design better translational studies for human diseases.
Area of Science:
- Immunology
- Translational Medicine
- Animal Models
Background:
- Humanized mice are crucial for studying human diseases in preclinical settings.
- Challenges exist in translating findings due to complex mouse-human cell interactions.
- Aging, irradiation, and immune reconstitution further complicate these models.
Purpose of the Study:
- To investigate the impact of age and irradiation on humanized mice.
- To analyze hematologic and behavioral changes in humanized mice.
- To provide data for improved translational study design.
Main Methods:
- Utilized humanized mice models.
- Assessed age- and irradiation-dependent effects.
- Monitored hematologic parameters, blood proteins, and body composition.
- Analyzed home cage behaviors, including locomotion, feeding, and drinking.
Main Results:
- Age and irradiation influenced the development of macrocytic hyperchromic anemia and myelodysplasia.
- Humanization contributed to hematologic abnormalities and reduced blood proteins.
- Human cell reconstitution affected locomotion patterns.
- Age-related variability in movement, feeding, and drinking behaviors was observed.
Conclusions:
- Age and irradiation significantly impact humanized mouse models, affecting hematology and behavior.
- Humanization introduces specific hematologic changes.
- Understanding these variables is essential for optimizing translational research using humanized mice.
