Damage to incisors after nonmyeloablative total body irradiation may complicate NOD/SCID models of hemopoietic stem cell transplantation.
Immunocompromised murine xenotransplantation models have become an important tool to study stem cell biology. One of the most common recipient strains used is the NOD/SCID mouse, which offers sufficient longevity to quantify moderate levels of engraftment. During pilot experiments, we noted incisor abnormalities 5 to 6 wk after nonmyeloablative doses of irradiation. Here we report a detailed examination of this phenomenon and propose possible explanations and management strategies. A total of 15 NOD/SCID mice received 3 Gy total body irradiation (TBI) and were monitored over 9 wk. A control group of 15 mice were treated in exactly the same way as the study mice except that they did not receive irradiation. A total of 9 TBI mice developed incisor abnormalities between days 40 and 50 after irradiation, resulting in rapid weight loss. No mice in the control group developed incisor abnormalities, however 3 were euthanized prematurely due to the development of thymic lymphoma. Upon development of incisor abnormalities and weight loss, 2 mice in the TBI group had their teeth trimmed and received soft food. Both mice made a rapid recovery and survived for the remainder of the study. The development of incisor abnormalities occurred in 2 substrains, and alterations in antibiotic use and supplementation of the vitamin content of feeds did not prevent the abnormalities. Investigators working with this model should be aware of this complication and modify protocols appropriately.
Larsen
Stephen R
SR
Gene and Stem Cell Therapy Program, Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, NSW, Australia.
Kingham
Jenny A
JA
Hayward
Marcus D
MD
Rasko
John E J
JE
D000818:Animals; D001835:Body Weight / Q000528:radiation effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D007180:Incisor / Q000473:pathology / Q000528:radiation effects*; D008136:Longevity / Q000528:radiation effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D014916:Whole-Body Irradiation / Q000009:adverse effects*