An ENU-induced mutant archive for gene targeting in rats

Mashimo, Tomoji; Yanagihara, Keiko; Tokuda, Satoko; Voigt, Birger; Takizawa, Akiko; Nakajima, Reiko; Kato, Megumi; Hirabayashi, Masumi; Kuramoto, Takashi; Serikawa, Tadao

doi:10.1038/ng0508-514

Cited by 79 publications

(74 citation statements)

References 10 publications

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“…They include discovering naturally occurring mutations and inducing mutations by random mutagenesis [21]. In addition, attempts have been made to collect mutations outside of the laboratory, from the field or fancy rat colonies; indeed, some inbred strains have been established from wild captured rats [11].…”

Section: Introductionmentioning

confidence: 99%

Genetic Analyses of Fancy Rat-Derived Mutations

et al. 2010

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Abstract:To collect rat mutations and increase the value of the rat model system, we introduced fancy-derived mutations to the laboratory and carried out genetic analyses. Six fancy rats were shipped from a fancy rat colony in the USA and used as founders. After initial crosses with a laboratory strain, TM/Kyo or PVG/Seac, inbreeding started and 6 partially inbred lines, including 2 sublines, were produced as Kyoto Fancy Rat Stock (KFRS) strains. During inbreeding, we isolated 9 mutations: 5 coat colors, American mink (am), Black eye (Be), grey (g), Pearl (Pel), siamese (sia); 1 coat pattern, head spot (hs); 2 coat textures, Rex (Re), satin (sat); and an ear pinnae malformation, dumbo (dmbo). Genetic analyses mapped 7 mutations to particular regions of the rat chromosomes (Chr): am to Chr 1, sia to Chr 1, sat to Chr 3, Re to Chr 7, g to Chr 8, dmbo to Chr 14, and hs to Chr 15. Candidate gene analysis revealed that a missense mutation in the tyrosinase gene, Ser79Pro, was responsible for sia. From mutant phenotypes and mapping positions, it is likely that all mutations isolated in this study were unique to the fancy rat. These findings suggest that fancy rat colonies are a good source for collecting rat mutations. The fancy-derived mutations, made available to biomedical research in the current study, will increase the scientific value of laboratory rats.

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Section: Introductionmentioning

confidence: 99%

Genetic Analyses of Fancy Rat-Derived Mutations

et al. 2010

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“…It probably is only a reverse genetic tool for most of the mammalian species, since no species other than the mouse have currently established ES cell lines. In fact, an ENU-based gene-driven mutagenesis system has already been started in the rat [18,32,36]. Another issue is the archiving of the G1 females, as described above under "ENU Mouse Mutagenesis."…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Also, HRM is often sensitive enough to distinguish between two different homozygous base substitutions and to detect the difference between one and two mutations in a given PCR product. Recently, Dr. Serikawa's group developed the MuT-POWER method, another sensitive and high-throughput heteroduplex detection system, which has been shown to be a very effective mutation discovery system for screening point mutations in the rat [18].…”

Section: High Throughput Mutation Discovery Systemsmentioning

confidence: 99%

ENU-Based Gene-Driven Mutagenesis in the Mouse: A Next-Generation Gene-Targeting System

et al. 2010

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Abstract:As a new mouse mutant resource, the RIKEN ENU-based gene-driven mutagenesis system in the mouse has been available to the research community since 2002. By using random base-substitution mutagenesis with ENU, a new reverse genetics infrastructure has been developed as a next-generation gene-targeting system. The construction of a largescale mutant mouse library and high-throughput mutation discovery systems were the keys making it practically feasible. The RIKEN mutant mouse library consists of ~10,000 G1 mice, within which 100-150 mutant strains have been established based on users' requests every year. Use of the system is very simple: users 1) download an application form from our web site and send to us, and 2) design the PCR primers for the target gene. Then, we screen the RIKEN mutant mouse library and report all the detected mutations to the user. From among the allelic series of discovered mutations, users decide which mutant strain(s) to analyze and request the live mutant strain for functional studies of the target gene. Users have been reporting various functional mutations in the RIKEN mutant mouse library: e.g., missense, knockout-type and even functional non-coding mutations. In the near future, next-generation re-sequencing systems should drastically enhance the utility of the ENUbased gene-driven mutagenesis not only for the mouse but also for other species.

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“…To overcome such a limitation, we have generated a large repository of ENu-induced mutations, called the Kyoto university Rat Mutant archive (KuRMa) [15]. DNa mutations in the repository can be efficiently screened with a high-throughput and low-cost assay based on the Mu-transposition reaction (MuT-PoWER).…”

Section: Kyoto University Rat Mutant Archive (Kurma)mentioning

confidence: 99%

“…Tissue organogenesis and trans-differentiation of stem cells are expected to be targets of study using these reporter gene transgenic rats. In addition to the rat strains, a set of sperm and DNa of 5,000 ENu mutagenized F344 G1 animals have been placed in the NBRP repository [15].…”

Section: National Bioresource Project-rat (Nbrp-rat)mentioning

confidence: 99%

National BioResource Project-Rat and Related Activities

et al. 2009

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Abstract:In order to establish a system to facilitate the systematic collection, preservation, and provision of laboratory rats (Rattus norvegicus) and their derivates, the National BioResource Project-Rat (NBRP-Rat) was launched in July 2002. By the end of 2008, more than 500 rat strains had been collected and preserved as live animals, embryos, or sperm. These rat resources are supplied to biomedical scientists in Japan as well as in other countries. This review article introduces NBRP-Rat and highlights the phenome project, recombinant inbred strains, BAC clone libraries, and the ENU-mutant archive, named the Kyoto University Rat Mutant Archive (KURMA). The future direction of rat resources are also discussed.

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An ENU-induced mutant archive for gene targeting in rats

Cited by 79 publications

References 10 publications

Genetic Analyses of Fancy Rat-Derived Mutations

Genetic Analyses of Fancy Rat-Derived Mutations

ENU-Based Gene-Driven Mutagenesis in the Mouse: A Next-Generation Gene-Targeting System

National BioResource Project-Rat and Related Activities

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