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

Caninized mice are feasible but require improved engraftment efficiency before reliable use in canine disease modeling.

This experimental study investigated the feasibility of creating 'caninized' mice by engrafting canine hematopoietic stem cells (HSCs) into immunodeficient NOD scid gamma (NSG) mice. Canine HSCs were isolated from donor dog bone marrow mononuclear cells using immunomagnetic sorting with an anti-canine CD34 antibody, achieving a median CD34+ cell purity of 87.6% compared to 2.5% in unsorted bone marrow. Fresh or overnight-cultured HSCs were administered intravenously to sublethally irradiated NSG mice 4 to 20 hours post-irradiation, with a median dose of 2.0 x 10^5 cells across 120 injected mice and 30 non-injected irradiated controls. Engraftment was assessed via serum canine IgM measurement, flow cytometric analysis, and immunohistochemical staining for T and B cells. Canine IgM was detectable in 49% of 94 surviving injected mice at 19 to 42 weeks post-irradiation, with a median IgM concentration of 310 ng/mL. Fresh HSCs produced higher serum canine IgM concentrations than overnight-cultured cells. Low numbers of canine leukocytes, T cells, and B cells were identified in the spleen and bone marrow. While the study demonstrates proof-of-concept that NSG mice can be engrafted with canine immune cells, engraftment efficiency was low. The authors conclude that creation of 'caninized' mice is feasible but requires further optimization before this model can reliably replicate canine immune function for disease modeling or therapeutic testing.

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