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A murine xenograft model for a transmissible cancer in Tasmanian devils
A Kreiss1, C Tovar, D L Obendorf
1Dr Menzies Research Institute, University of Tasmania, Hobart, Tasmania 7000, Australia. akreiss@utas.edu.au
Abstract:
The number of Tasmanian devils in the wild is rapidly declining owing to a transmissible cancer, devil facial tumor disease (DFTD). Although progress has been made to understand the spread of this disease, crucial research on the pathogenesis of DFTD has been limited because of the threatened status of the host species. Here, the authors describe the development of a NOD/SCID (nonobese diabetic / severe combined immunodeficiency) mouse model that reproduces DFTD and provides a much-needed model to undertake studies into this intriguing transmissible cancer. Histologically, the DFTD produced in NOD/SCID mice (xenografted DFTD) was indistinguishable from the DFTD identified in Tasmanian devils. At the protein level, all xenografted DFTD tumors expressed periaxin, a marker that confirmed the diagnosis of DFTD. The karyotype of DFTD in NOD/SCID mice reproduced similar chromosomal alterations as seen in diseased devils. Furthermore, each NOD/SCID mouse inoculated with cultured DFTD tumor cells developed tumors, whereas DFTD did not develop in any of the inoculated immune-competent BALB/c mice.
Insights
Researchers developed a mouse model to study devil facial tumor disease (DFTD), a deadly cancer threatening Tasmanian devils. This new model allows crucial research into DFTD pathogenesis, aiding conservation efforts.
Area of Science:
- Veterinary Pathology
- Cancer Biology
- Immunology
Background:
- Devil facial tumor disease (DFTD) is a contagious cancer causing rapid population decline in Tasmanian devils.
- Research into DFTD pathogenesis is limited by the endangered status of Tasmanian devils, hindering in-vivo studies.
Purpose of the Study:
- To develop a reliable animal model for studying DFTD.
- To enable detailed investigations into the mechanisms and progression of this transmissible cancer.
Main Methods:
- Development of a xenograft model using NOD/SCID mice.
- Histological and protein-level analysis of tumors in the mouse model.
- Karyotype analysis of DFTD in mice compared to diseased devils.
- Tumor development assessment in both immunodeficient (NOD/SCID) and immune-competent (BALB/c) mice.
Main Results:
- NOD/SCID mice successfully developed xenografted DFTD, histologically identical to naturally occurring DFTD.
- Periaxin expression confirmed DFTD diagnosis in xenografted tumors.
- Karyotype analysis revealed similar chromosomal alterations in mouse-derived DFTD as in devils.
- Tumors formed in NOD/SCID mice, but not in immune-competent BALB/c mice.
Conclusions:
- The NOD/SCID mouse model effectively reproduces DFTD, providing a vital tool for research.
- This model overcomes limitations posed by the host species' threatened status, facilitating pathogenesis studies.
- Further research using this model can advance understanding and potential treatments for DFTD.
