Toward creating "caninized" mice: reconstitution of canine immune cells in immunodeficient mice.

OBJECTIVE

To generate "caninized" mice that could be used for investigating canine diseases and testing new therapies.

METHODS

In this experimental study, canine hematopoietic stem cells (HSCs) were isolated from bone marrow mononuclear cells from donor dogs using immunomagnetic sorting and an anti-canine CD34 antibody. Fresh or overnight-cultured HSCs were administered IV into sublethally irradiated immunodeficient mice (NOD scid γ strain) 4 to 20 hours after irradiation (median dose, 2.0 X 105 cells; n = 120) with noninjected irradiated controls (30). Engraftment was assessed by serum canine immunoglobulin M (IgM) measurement and flow cytometric analysis for canine leukocytes and immunohistochemical staining for T and B cells.

RESULTS

HSCs were enriched after sorting (median CD34+ cells, 87.6% vs 2.5% in bone marrow mononuclear cells). Canine IgM was measurable in sera of 49% of 94 surviving injected mice 19 to 42 weeks after irradiation (median IgM, 310 ng/mL; range, 18 to > 8,400 ng/mL). Higher serum canine IgM concentrations were detected in mice injected with fresh versus overnight-cultured HSCs. Low numbers of canine leukocytes and T and B cells were identified in the spleen and bone marrow with flow cytometry or immunohistochemistry.

CONCLUSIONS

NOD scid γ mice can be engrafted with canine immune cells.

CLINICAL RELEVANCE: The creation of "caninized" mice is feasible, but efficiency of engraftment was low and requires further optimization before these mice can be used to model canine disease.