HLA transgenic mice: application in reproducing idiosyncratic drug toxicity

Abstract

Various types of transgenic mice carrying either class I or II human leukocyte antigen (HLA) molecules are readily available, and reports describing their use in a variety of studies have been published for more than 30 years. Examples of their use include the discovery of HLA-specific antigens against viral infection as well as the reproduction of HLA-mediated autoimmune diseases for the development of therapeutic strategies. Recently, HLA transgenic mice have been used to reproduce HLA-mediated idiosyncratic drug toxicity (IDT), a rare and unpredictable adverse drug reaction that can result in death. For example, abacavir-induced IDT has successfully been reproduced in HLA-B*57:01 transgenic mice. Several reports using HLA transgenic mice for IDT have proven the utility of this concept for the evaluation of IDT using various HLA allele combinations and drugs. It has become apparent that such models may be a valuable tool to investigate the mechanisms underlying HLA-mediated IDT. This review summarizes the latest findings in the area of HLA transgenic mouse models and discusses the current challenges that must be overcome to maximize the potential of this unique animal model.

Keywords:

• HLA
• idiosyncratic drug toxicity
• transgenic mice
• immunotoxicity
• animal model

Acknowledgments

The authors thank Editage (www.editage.com) for English language editing.

Disclosure statement

The authors declare no conflicts of interests in association with this manuscript.

Additional information

Funding

This work was supported by the Japan Society for the Promotion of Science (19H03386).