Influence of age, irradiation and humanization on NSG mouse phenotypes.
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.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Jaclyn S
JS
Knibbe-Hollinger
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Natasha R
NR
Fields
Department of Internal Medicine, Geriatrics Division, 986155 Nebraska Medical Center, Omaha, NE 68198-6155, USA.
Tammy R
TR
Chaudoin
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Adrian A
AA
Epstein
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Edward
E
Makarov
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Sidra P
SP
Akhter
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Santhi
S
Gorantla
Department of Internal Medicine, Geriatrics Division, 986155 Nebraska Medical Center, Omaha, NE 68198-6155, USA.
Stephen J
SJ
Bonasera
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Howard E
HE
Gendelman
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE 68198-5880, USA lpoluekt@unmc.edu.
Larisa Y
LY
Poluektova
Behavior; Body mass composition; Chemistry; Circadian rhythm; Hematology; Locomotion; Mouse home cage monitoring; NSG mice; Time