Influence of age, irradiation and humanization on NSG mouse phenotypes
Jaclyn S. Knibbe-Hollinger,
Natasha R. Fields,
Tammy R Chaudoin,
Adrian A. Epstein,
Edward Makarov,
Sidra P. Akhter,
Santhi Gorantla,
Stephen J. Bonasera,
Howard E. Gendelman,
Larisa Y. Poluektova
Affiliations
Jaclyn S. Knibbe-Hollinger
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
Natasha R. Fields
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
Tammy R Chaudoin
Department of Internal Medicine, Geriatrics Division, 986155 Nebraska Medical Center, Omaha, NE 68198-6155, USA
Adrian A. Epstein
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
Edward Makarov
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
Sidra P. Akhter
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
Santhi Gorantla
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
Stephen J. Bonasera
Department of Internal Medicine, Geriatrics Division, 986155 Nebraska Medical Center, Omaha, NE 68198-6155, USA
Howard E. Gendelman
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
Larisa Y. Poluektova
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA
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.