New homozygous gpt delta transgenic rat strain improves an efficiency of the in vivo mutagenicity assay

Genes and Environment

Hiroyuki Hayashi¹  Shigeo Yokose²  Sho Fujiwara²  Hisayoshi Takagi²  Akiko Ukai³  Kenichi Masumura³  Tomoko Ando³  Masamitsu Honma³  Xinyue You⁴  Takehiko Nohmi⁵  Takayoshi Suzuki⁶ 

[1] Biologics Business Planning & Operation Dept, Meiji Seika Pharma Co., Ltd;Biotechnical Center, Japan SLC, Inc.;Division of Genetics and Mutagenesis, National Institute of Health Sciences;Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences;Division of Pathology, National Institute of Health Sciences;School of Public Health, Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine;

关键词: gpt delta transgenic rat;    gpt assay;    Spi− assay;    mutant frequency;    mutation spectrum;   

DOI  :  10.1186/s41021-021-00195-1

来源: DOAJ

【 摘 要 】

Abstract Background Gene mutation assays in transgenic rodents are useful tools to investigate in vivo mutagenicity in a target tissue. Using a lambda EG10 transgene containing reporter genes, gpt delta transgenic mice and rats have been developed to detect point mutations and deletions. The transgene is integrated in the genome and can be rescued through an in vitro packaging reaction. However, the packaging efficiency is lower in gpt delta rats than in mice, because of the transgene in gpt delta rats being heterozygous and in low copy number. To improve the packaging efficiency, we herein describe a newly developed homozygous gpt delta rat strain. Results The new gpt delta rat has a Wistar Hannover background and has been successfully maintained as homozygous for the transgene. The packaging efficiency in the liver was 4 to 8 times higher than that of existing heterozygous F344 gpt delta rats. The frequency of gpt point mutations significantly increased in the liver and bone marrow of N-nitroso-N-ethylurea (ENU)- and benzo[a]pyrene (BaP)-treated rats. Spi− deletion frequencies significantly increased in the liver and bone marrow of BaP-treated rats but not in ENU-treated rats. Whole genome sequencing analysis identified ≥ 30 copies of lambda EG10 transgenes integrated in rat chromosome 1. Conclusions The new homozygous gpt delta rat strain showed a higher packaging efficiency, and could be useful for in vivo gene mutation assays in rats.

【 授权许可】

Unknown