Spontaneous Hind Limb Paralysis Due to Acute Precursor B Cell Leukemia in RAG1-deficient Mice

RAG1-deficient mice are a frequently used immunodeficient mouse strain lacking mature lymphocytes. Apart from an elevated risk for infections, no predispositions for diseases of this strain have been described so far. We here report a high incidence of spontaneous pro B cell leukemia resulting in hind limb paralysis in our colony of RAG1-deficient mice. At an age of 7–13 months, animals developed hind limb paralysis and rapid decrease of the overall health condition leading to the need of euthanasia. Histological and flow cytometric analyses as well as micro-computed tomography (micro-CT) scans revealed CD45(+) CD19(+) IgM(−) cell infiltrates in the spleen, the bone marrow, and the spinal canal. Monthly blood sampling and screening for CD19(+) blast frequency in the peripheral blood was successfully established for monitoring of leukemia development before symptom onset. We conclude that facilities that breed RAG1-deficient mice should be aware of the risk of leukemia development in this strain and recommend to implement regular blood sampling for aged RAG1-deficient animals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12031-022-02025-7.