“Passenger gene” problem in transgenic C57BL/6 mice used in hearing research

Jun Suzuki, Hitoshi Inada, Chul Han, Mi Jung Kim, Ryuichi Kimura, Yusuke Takata, Yohei Honkura, Yuji Owada, Tetsuaki Kawase, Yukio Katori, Shinichi Someya, Noriko Osumi

研究成果: Article査読

抄録

Despite recent advances in genome engineering technologies, traditional transgenic mice generated on a mixed genetic background of C57BL/6 and 129/Sv mice remain widely used in age-related hearing loss (AHL) research, since C57BL/6 mice exhibit early onset and progression of AHL due to a mutation in cadherin 23-encoding gene (Cdh23753G>A). In these transgenic mice, backcrossing for more than 10 generations results in replacement of the donor background (129/Sv) with that of the recipient (C57BL/6), so that approximately 99.9% of genes are C57BL/6-derived and are considered congenic. However, the regions flanking the target gene may still be of 129/Sv origin, creating a so-called “passenger gene problem” where the normal 129/Sv-derived Cdh23753G allele can travel with the target gene. In this study, we investigated the role of fatty acid-binding protein 7 (Fabp7), which is important for cellular uptake and intracellular trafficking of fatty acids in the cochlea, using traditional Fabp7 knockout (KO) mice on the C57BL/6 background. We found that Fabp7 KO mice showed delayed AHL progression and milder cochlear degeneration. However, the genotype of the Cdh23 region flanking Fabp7 was still that of 129/Sv origin (Cdh23753GG). Our findings reveal the potential risk of contamination for traditional transgenic mice generated on the C57BL/6 background.

本文言語English
ページ(範囲)6-15
ページ数10
ジャーナルNeuroscience Research
158
DOI
出版ステータスPublished - 2020 9

ASJC Scopus subject areas

  • Neuroscience(all)

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