A novel mouse model of adult T-cell leukemia cell invasion into the spinal cord

Takeo Ohsugi; Shuhei Tanaka; Keigo Iwasaki; Yusuke Nagano; Tomohiro Kozako; Kazuya Matsuda; Takuya Hirose; Kazushige Takehana

doi:10.1002/ame2.12053

A novel mouse model of adult T-cell leukemia cell invasion into the spinal cord

Animal Model Exp Med. 2019 Jan 29;2(1):64-67. doi: 10.1002/ame2.12053. eCollection 2019 Mar.

Authors

Takeo Ohsugi¹, Shuhei Tanaka¹, Keigo Iwasaki¹, Yusuke Nagano¹, Tomohiro Kozako², Kazuya Matsuda³, Takuya Hirose⁴, Kazushige Takehana⁴

Affiliations

¹ Department of Laboratory Animal Sciences School of Veterinary Medicine Rakuno Gakuen University Ebetsu Hokkaido Japan.
² Faculty of Pharmaceutical Sciences Department of Biochemistry Fukuoka University Fukuoka Japan.
³ Department of Veterinary Pathology School of Veterinary Medicine Rakuno Gakuen University Ebetsu Hokkaido Japan.
⁴ Department of Veterinary Microanatomy School of Veterinary Medicine Rakuno Gakuen University Ebetsu Hokkaido Japan.

Abstract

Adult T-cell leukemia (ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system (CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly (I.M.) at 5 weeks of age, 8 (80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously (S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV-1-specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV-1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.

Keywords: NOD.Cg‐PrkdcscidIl2rgtm1Wjl/SzJ mice; adult T‐cell leukemia (ATL); central nervous system (CNS); human T‐cell leukemia virus type I (HTLV‐1); mice.