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

J Mol Neurosci. 2022 Aug;72(8):1646-1655. doi: 10.1007/s12031-022-02025-7. Epub 2022 May 18.

Abstract

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.

Keywords: Hematologic Malignancy; Micro-CT; Paralysis; Pro B cell leukemia; RAG1-deficient mice.

MeSH terms

  • Animals
  • Homeodomain Proteins / genetics
  • Mice
  • Paralysis* / etiology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / complications
  • X-Ray Microtomography

Substances

  • Homeodomain Proteins
  • RAG-1 protein