c-MAF deletion in adult C57BL/6J mice induces cataract formation and abnormal differentiation of lens fiber cells

  • Fujino Mitsunori
    Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
  • Tagami Asuka
    Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
  • Ojima Masami
    Laboratory Animal Resource Center (LARC), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
  • Mizuno Seiya
    Laboratory Animal Resource Center (LARC), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
  • Abdellatif Ahmed M.
    Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
  • Kuno Akihiro
    Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
  • Takahashi Satoru
    Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan Laboratory Animal Resource Center (LARC), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan

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Abstract

<p> The transcription factor c-MAF is a member of the large MAF family, members of which possess transactivation and bZIP domains. c-MAF plays an important role in lens formation, T-lymphocyte differentiation, hypertrophic chondrocyte differentiation, and kidney development in mouse embryos. However, because homozygous deletion of c-Maf in C57BL/6J mice causes embryonic lethality, the functions of c-MAF in adult mice remain largely uninvestigated. To address this issue, we generated c-Maf floxed (c-Maffl/fl) C57BL/6J mice and established tamoxifen-inducible c-Maf knockout mice (c-Maffl/fl; CAG-Cre-ERTM mice, c-MafΔTAM). After tamoxifen injection, adult c-MafΔTAM mice showed successful deletion of c-Maf protein and developed severe cataracts; cataracts are also seen in human patients who have mutations in the c-MAF DNA binding domain. Furthermore, adult c-MafΔTAM mice exhibited abnormal lens structure and impaired differentiation of lens fiber cells. In summary, we established c-Maffl/fl and c-MafΔTAM C57BL/6J mice, which can be useful animal models for the investigation of c-MAF function in various developmental stages and can also be used as a disease model for cataracts.</p>

Journal

  • Experimental Animals

    Experimental Animals 69 (2), 242-249, 2020

    Japanese Association for Laboratory Animal Science

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