1. 'Passenger gene' problem in transgenic C57BL/6 mice used in hearing research
- Author
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Shinichi Someya, Tetsuaki Kawase, Yusuke Takata, Yohei Honkura, Ryuichi Kimura, Yuji Owada, Jun Suzuki, Yukio Katori, Noriko Osumi, Hitoshi Inada, Mi-Jung Kim, and Chul Han
- Subjects
0301 basic medicine ,C57BL/6 ,Genetically modified mouse ,Transgene ,Congenic ,Mice, Transgenic ,medicine.disease_cause ,Mice ,03 medical and health sciences ,0302 clinical medicine ,CDH23 ,Hearing ,medicine ,Animals ,Gene ,Mutation ,biology ,General Neuroscience ,General Medicine ,Presbycusis ,FABP7 ,Cadherins ,biology.organism_classification ,Molecular biology ,Cochlea ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2020