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Establishment of germline-competent embryonic stem cell lines from the MSM/Ms strain

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Abstract

MSM/Ms is an inbred mouse strain established from the Japanese wild mouse, Mus musculus molossinus, which has been phylogenetically distinct from common laboratory mouse strains for about 1 million years. The nucleotide substitution rate between MSM/Ms and C57BL/6 is estimated to be 0.96%. MSM/Ms mice display unique characteristics not observed in the commonly used laboratory strains, including an extremely low incidence of tumor development, high locomotor activity, and resistance to high-fat-diet-induced diabetes. Thus, functional genomic analyses using MSM/Ms should provide a powerful tool for the identification of novel phenotypes and gene functions. We report here the derivation of germline-competent embryonic stem (ES) cell lines from MSM/Ms blastocysts, allowing genetic manipulation of the M. m. molossinus genome. Fifteen blastocysts were cultured in ES cell medium and three ES lines, Mol/MSM-1, -2, and -3, were established. They were tested for germline competency by aggregation with ICR morulae and germline chimeras were obtained from all three lines. We also injected Mol/MSM-1 ES cells into blastocysts of ICR or C57BL/6 × BDF1 mice and found that blastocyst injection resulted in a higher production rate of chimeric mice than did aggregation. Furthermore, Mol/MSM-1 subclones electroporated with a gene trap vector were also highly efficient at producing germline chimeras using C57BL/6 × BDF1 blastocyst injection. This Mol/MSM-1 ES line should provide an excellent new tool allowing the genetic manipulation of the MSM/Ms genome.

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References

  • Abe K, Noguchi H, Tagawa K, Yuzuriha M, Toyoda A et al (2004) Contribution of Asian mouse subspecies Mus musculus molossinus to genomic constitution of strain C57BL/6J, as defined by BAC-end sequence-SNP analysis. Genome Res 14:2439–2447

    Article  PubMed  Google Scholar 

  • Araki K, Imaizumi T, Sekimoto T, Yoshinobu K, Yoshimuta J et al (1999) Exchangeable gene trap using the Cre/mutated lox system. Cell Mol Biol (Noisy-le-grand) 45:737–750

    CAS  Google Scholar 

  • Bonhomme F, Guénet JL (1996) The laboratory mouse and its wild relatives. In: Lyon MF, Rastan S, Brown SDM (eds) Genetic variants and strain of the laboratory mouse. Oxford University Press, Oxford, pp 1577–1596

    Google Scholar 

  • Cheng J, Dutra A, Takesono A, Garrett-Beal L, Schwartzberg PL (2004) Improved generation of C57BL/6J mouse embryonic stem cells in a defined serum-free media. Genesis 39:100–104

    Article  PubMed  Google Scholar 

  • Fujiyama A, Watanabe H, Toyoda A, Taylor TD, Itoh T et al (2002) Construction and analysis of a human-chimpanzee comparative clone map. Science 295:131–134

    Article  PubMed  Google Scholar 

  • Kobayashi M, Ohno T, Tsuchiya T, Horio F (2004) Characterization of diabetes-related traits in MSM and JF1 mice on high-fat diet. J Nutr Biochem 15:614–621

    Article  CAS  PubMed  Google Scholar 

  • Koide T, Moriwaki K, Ikeda K, Niki H, Shiroishi T (2000) Multi-phenotype behavioral characterization of inbred strains derived from wild stocks of Mus musculus. Mamm Genome 11:664–670

    Article  CAS  PubMed  Google Scholar 

  • Lawitts JA, Biggers JD (1993) Culture of preimplantation embryos. In: Wasserman PM, Depamphilis ML (eds) Methods in enzymology, vol 225. Academic Press, San Diego, CA, pp 153–164

    Google Scholar 

  • Miyashita N, Moriwaki K (1987) H-2-controlled genetic susceptibility to pulmonary adenomas induced by urethane and 4-nitroquinoline 1-oxide in A/Wy congenic strains. Jpn J Cancer Res 78:494–498

    CAS  PubMed  Google Scholar 

  • Moriwaki K, Shiroishi T, Yonekawa H (1994) Genetics in wild mice. Japan Scientific Societies Press/Karger, Tokyo/Basel

    Google Scholar 

  • Nagy A, Gocza E, Diaz EM, Prideaux VR, Ivanyi E et al (1990) Embryonic stem cells alone are able to support fetal development in the mouse. Development 110:815–821

    CAS  PubMed  Google Scholar 

  • Nagy A, Gertsenstein M, Vintersten K, Behringer R (2003) Manipulating the mouse embryo. A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

    Google Scholar 

  • Nakanishi M, Tazawa H, Tsuchiya N, Sugimura T, Tanaka T et al (2007) Mouse strain differences in inflammatory responses of colonic mucosa induced by dextran sulfate sodium cause differential susceptibility to PhIP-induced large bowel carcinogenesis. Cancer Sci 98:1157–1163

    Article  CAS  PubMed  Google Scholar 

  • Nakao K, Nakagata N, Katsuki M (1997) Simple and efficient vitrification procedure for cryopreservation of mouse embryos. Exp Anim 46:231–234

    Article  CAS  PubMed  Google Scholar 

  • Okumoto M, Mori N, Miyashita N, Moriwaki K, Imai S et al (1995) Radiation-induced lymphomas in MSM, (BALB/cHeA × MSM) F1 and (BALB/cHeA × STS/A) F1 hybrid mice. Exp Anim 44:43–48

    Article  CAS  PubMed  Google Scholar 

  • Peli J, Schmoll F, Laurincik J, Brem G, Schellander K (1996) Comparison of aggregation and injection techniques in producing chimeras with embryonic stem cells in mice. Theriogenology 45:833–842

    Article  CAS  PubMed  Google Scholar 

  • Robertson EJ (1987) Embryo-derived stem cell lines. In: Robertson EJ (ed) Teratocarcinomas and embryonic stem cells. A practical approach. IRL Press, Oxford, pp 71–112

    Google Scholar 

  • Shimizukawa R, Sakata A, Hirose M, Takahashi A, Iseki H et al (2005) Establishment of a new embryonic stem cell line derived from C57BL/6 mouse expressing EGFP ubiquitously. Genesis 42:47–52

    Article  CAS  PubMed  Google Scholar 

  • Shinmen A, Honda A, Ohkawa M, Hirose M, Ogonuki N et al (2007) Efficient production of intersubspecific hybrid mice and embryonic stem cells by intracytoplasmic sperm injection. Mol Reprod Dev 74:1081–1088

    Article  CAS  PubMed  Google Scholar 

  • Taniwaki T, Haruna K, Nakamura H, Sekimoto T, Oike Y et al (2005) Characterization of an exchangeable gene trap using pU-17 carrying a stop codon-beta geo cassette. Dev Growth Differ 47:163–172

    Article  CAS  PubMed  Google Scholar 

  • Tokunaga T, Tsunoda Y (1992) Efficacious production of viable germ-line chimeras between embryonic stem (ES) cells and 8-cell stage embryos. Dev Growth Differ 34:561–566

    Article  Google Scholar 

  • Yonekawa H, Moriwaki K, Gotoh O, Miyashita N, Matsushima Y et al (1988) Hybrid origin of Japanese mice “Mus musculus molossinus”: evidence from restriction analysis of mitochondrial DNA. Mol Biol Evol 5:63–78

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by KAKENHI (A) (17200028) and (B) (19300149) from the Japan Society for the Promotion of Science (JSPS). The MSM/Ms mouse strain (RBRC00209) was provided by RIKEN BRC, which is a participant in the National Bio-Resource Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. We thank Dr. M. Muta, Ms. Y. Tsuruta, and K. Haruna for their technical assistance, and the Center for Animal Resources and Development for the care of the animals used in this study.

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Correspondence to Ken-ichi Yamamura.

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Araki, K., Takeda, N., Yoshiki, A. et al. Establishment of germline-competent embryonic stem cell lines from the MSM/Ms strain. Mamm Genome 20, 14–20 (2009). https://doi.org/10.1007/s00335-008-9160-7

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  • DOI: https://doi.org/10.1007/s00335-008-9160-7

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