Characterization of Immunodeficient Mouse Models

Leakiness in SCID mouse models refers to the occasionally productive VDJ rearrangement leading to clonal expansion of these limited B and T cell clones. The rate and extent of leakiness in immunodeficient models is a factor of age as well as housing environment and the background strain of the model. In the current study, serum IgG was used to determine the extent of leakiness in various immunodeficient mouse models; survival and lymphoma incidence was also analyzed. Male and female (n=23–26) C.B‐17‐SCID, NOD SCID, SCID Beige, SHrN®, Beige Nude XID and Nude mice were housed in flexible film isolators. Blood was collected and analyzed using dried blood spot technology at 12, 16, 20 and 24 weeks of age for IgG concentration analysis using multiplex fluorescent immunoassay. The leakiness threshold was set at 5 μg/mL of IgG for analysis. At 24 weeks of age, necropsies were performed to determine incidence of lymphoma. At 24 wk of age, the SHrN® model had the smallest percentage of leaky animals followed closely by the NOD SCID. Beige Nude XID mice display an age associated increase in serum IgG levels as well as an increasing percentage of animals above the 5 μg/mL threshold from 12–24 weeks of age. Nude mice also show increases in IgG from 12 to 24 weeks of age. The NOD SCID and SHrN® mice had the lowest survival rate at 24 weeks; however, survivability in all models was greater than or equal to 79%. There is a positive correlation between the percentage of leaky animals and survival in males and females across all models. The C.B17‐SCID shows low incidence of lymphoma at 24 weeks of age whereas the NOD SCID model has the highest incidence of lymphoma but when the hairless mutation is crossed onto the NOD SCID mouse to create the SHrN®, incidence of lymphoma is decreased. This is the first study reporting IgG concentration in multiple immunodeficient models to examine leakiness as well as 24 week survival and lymphoma incidence. Additional studies measuring immune cell activity and function will be useful to further characterize immunodeficient models; however, these data will be valuable information in determining the best model for xenograft research.