Transcriptome analysis and germ-cell development analysis of mice in the space (Mouse Epigenetics) - 03.06.19

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
From bacteria to humans, organisms change when they spend time in space, and some of these changes are related to modifications in gene expression and in the molecular coating that surrounds cells’ DNA. The Transcriptome analysis and germ-cell development analysis of mice in the space (Mouse Epigenetics) investigation studies altered gene expression patterns in the organs of male mice that spend one month in space, and also examines changes in the DNA of their offspring. Results from the investigation identify genetic alterations that happen after exposure to the microgravity environment of space.
Science Results for Everyone
Artificial gravity beats no gravity. Researchers investigated effects of gravity on musculoskeletal health in mice using the Multiple Artificial-gravity Research System, or MARS, aboard the space station. Mice exposed to microgravity showed higher water consumption, greater muscle loss leading to lower body mass, and increasingly reduced bone density, while mice exposed to simulated Earth gravity showed no such effects. This suggests reduced gravity is the cause of health issues seen in astronauts. The MARS platform enables experiments using different levels of gravity in space, supporting future space exploration by providing insights into gravity’s effects on biological processes.

The following content was provided by Satoru Takahashi, M.D., Ph.D., Takashi Shiga, Ph.D., and is maintained in a database by the ISS Program Science Office.
Information provided courtesy of the Japan Aerospace and Exploration Agency (JAXA).
Experiment Details

OpNom: Mouse Epigenetics

Principal Investigator(s)
Satoru Takahashi, M.D., Ph.D., Department of Genome Biology, Faculty of Medicine , University of Tsukuba, Tsukuba, Ibaraki, Japan
Takashi Shiga, Ph.D., University of Tsukuba, Tsukuba, Ibaraki, Japan

Kenich Yagami, Ph.D., University of Tsukuba, Tsukuba, Ibaraki, Japan
Nobuaki Yoshida, M.D., The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan
Masahito Ikawa, Ph.D., Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Akira Kurisaki, Ph.D., National Institute for Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
Akiyoshi Fukamizu, Ph.D., University of Tsukuba, Tsukuba, Ibaraki, Japan
Hiroshi Asahara, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
Hironobu Morita, M.D., Ph.D., Gifu University, Gifu, Japan
Takashi Kudo, Ph.D., University of Tsukuba, Tsukuba, Ibaraki, Japan

Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, Tsukuba, Ibaraki , Japan

Sponsoring Space Agency
Japan Aerospace Exploration Agency (JAXA)

Sponsoring Organization
Japan Aerospace Exploration Agency

Research Benefits
Scientific Discovery

ISS Expedition Duration
September 2015 - March 2016; March 2016 - September 2016

Expeditions Assigned

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • Under microgravity conditions in space, unusual gene expression patterns in normal body cells can be induced by various stresses due of the lack of gravity that would otherwise be available on Earth. Additionally, various stress inducing conditions, including cosmic radiation, are also expected to induce unexpected genomic or epigenomic changes to the genes in germ (reproductive) cells.
  • The Transcriptome analysis and germ-cell development analysis of mice in the space (Mouse Epigenetics) investigation looks at the long-term effects of the space environment on gene expression patterns, and on epigenetic changes of DNA in different organs, are to be identified using model animals. Also, the impact of the space environment on mammalian germ cells is to be clarified by the production of offspring using the sperm cells exposed to the space environment.

Information Pending

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Space Applications
The investigation sends 12 male mice to the International Space Station (ISS), where they will live for 30 days before being sent back to Earth. After their return, scientists remove their internal organs for detailed study and harvest their sperm cells, which are to be used for in-vitro fertilization of new mouse embryos. Analysis of the male mice and their offspring reveals the long-term effects of space travel at a molecular level, including changes to gene expression and epigenetic modification. In addition, the mouse habitat becomes an important piece of equipment for future mammal studies on the ISS.

Earth Applications
Results from this investigation describe spaceflight’s long-term effects on genetic activity, from changes in gene expression in individual organs to changes in DNA that can be inherited later. Mice are an important model for human health, so information from this investigation serves as a proxy for understanding how the human body changes in space, and how those changes may affect later generations.

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Operational Requirements and Protocols
Information Pending

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Decadal Survey Recommendations

Information Pending

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Results/More Information

The primary goal in the Mouse Epigenetics investigation is to study altered gene expression patterns in the organs of male mice that spend one month in space, as well as the changes in the DNA of their offspring. The first publication to arise from this study reports on the effects of artificial gravity from the on-orbit centrifuge on maintaining muscle and bone health of the ISS mice. Over an ISS duration of 35 days, mice that underwent artificial gravity exposure via regular continuous centrifugation at a 1-g (Earth-simulated) level did not display a significant decrease in soleus and gastrocnemius muscle weight and bone loss, unlike mice on the ISS that received no centrifugation. Both mice in artificial gravity and microgravity ate about the same during spaceflight; however, the microgravity mice showed higher water consumption. Upon return to Earth, the mice underwent a rotarod test, which is a standard laboratory test used to determine physical fitness of the mice. Both mouse groups exposed to spaceflight displayed less physical fitness than ground control mice, suggesting that despite the muscle and bone maintenance, spaceflight impaired motor coordination in both artificial gravity and microgravity mice. Overall, these findings provide results that will contribute to an understanding of physiological changes associated with artificial gravity exposure when considering it as a potential tool to maintain human health for long-duration spaceflight. 

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Results Publications

    Mao XW, Byrum S, Nishiyama NC, Pecaut MJ, Sridharan V, Boerma M, Tackett AJ, Shiba D, Shirakawa M, Takahashi S, Delp MD.  Impact of spaceflight and artificial gravity on the mouse retina: Biochemical and proteomic analysis. International Journal of Molecular Sciences. 2018 August 28; 19(9): 2546. DOI: 10.3390/ijms19092546. PMID: 30154332.

    Shiba D, Mizuno H, Yumoto A, Shimomura M, Kobayashi H, Morita H, Shimbo M, Hamada M, Kudo T, Shinohara M, Asahara H, Shirakawa M, Takahashi S.  Development of new experimental platform ‘MARS’—Multiple Artificial-gravity Research System—to elucidate the impacts of micro/partial gravity on mice. Scientific Reports. 2017 September 7; 7(1): 10837. DOI: 10.1038/s41598-017-10998-4. PMID: 28883615.

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Ground Based Results Publications

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ISS Patents

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Related Publications

    Horie K, Kudo T, Yoshinaga R, Akiyama N, Sasanuma H, Kobayashi TJ, Shimbo M, Jeon H, Miyao T, Miyauchi M, Shirakawa M, Shiba D, Yoshida N, Muratani M, Takahashi S, Akiyama T.  Long-term hindlimb unloading causes a preferential reduction of medullary thymic epithelial cells expressing autoimmune regulator (Aire). Biochemical and Biophysical Research Communications. 2018 June; 501(3): 745-750. DOI: 10.1016/j.bbrc.2018.05.060. PMID: 29753741.

    Shimbo M, Kudo T, Hamada M, Jeon H, Imamura Y, Asano K, Okada R, Tsunakawa Y, Mizuno S, Yagami K, Ishikawa C, Li H, Shiga T, Ishida J, Hamada J, Murata K, Ishimura T, Hashimoto M, Fukamizu A, Yamane M, Ikawa M, Morita H, Shinohara M, Asahara H, Akiyama T, Akiyama N, Sasanuma H, Yoshida N, Zhou R, Wang Y, Ito T, Kokubu Y, Noguchi TK, Ishimine H, Kurisaki A, Shiba D, Mizuno H, Shirakawa M, Ito N, Takeda S, Takahashi S.  Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies. Experimental Animals. 2016 January 28; epub: 45 pp. DOI: 10.1538/expanim.15-0077. PMID: 26822934.

    Morita H, Obata K, Abe C, Shiba D, Shirakawa M, Kudo T, Takahashi S.  Feasibility of a short-arm centrifuge for mouse hypergravity experiments. PLOS ONE. 2015 July 29; 10(7): e0133981. DOI: 10.1371/journal.pone.0133981. PMID: 26221724.

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Related Websites

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NASA Images: ISS048E042371 - Documentation of a Glove Box set up on the Kobairo Rack (JPM1F3) for Mouse Epigenetics experiment. Photo taken in the Kibo Japanese Experiment Pressurized Module (JPM).

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