Mice harboring an MCTO mutation exhibit renal failure resembling nephropathy in human patients

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著者

    • TSUNAKAWA Yuki
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba|Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba
    • MORITO Naoki
    • Department of Nephrology, Faculty of Medicine, University of Tsukuba
    • TAKAHASHI Satoru
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba|Laboratory Animal Resource Center (LARC), Faculty of Medicine, University of Tsukuba|International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba|Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba
    • HAMADA Michito
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba
    • MATSUNAGA Yurina
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba
    • FUSEYA Sayaka
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba|Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba
    • JEON Hyojung
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba
    • USUI Toshiaki
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba|Department of Nephrology, Faculty of Medicine, University of Tsukuba
    • KANAI Maho
    • Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba|Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba
    • MIZUNO Seiya
    • Laboratory Animal Resource Center (LARC), Faculty of Medicine, University of Tsukuba

抄録

<p>Multicentric carpotarsal osteolysis (MCTO) is a condition involving progressive osteolysis of the carpal and tarsal bones that is associated with glomerular sclerosis and renal failure (MCTO nephropathy). Previous work identified an autosomal dominant missense mutation in the transactivation domain of the transcription factor <i>MAFB</i> as the cause of MCTO. Several methods are currently used for MCTO nephropathy treatment, but these methods are invasive and lead to severe side effects, limiting their use. Therefore, the development of alternative treatments for MCTO nephropathy is required; however, the pathogenesis of MCTO <i>in vivo</i> is unclear without access to a mouse model. Here, we report the generation of an MCTO mouse model using the CRISPR/Cas9 system. These mice exhibit nephropathy symptoms that are similar to those observed in MCTO patients. <i>Mafb<sup>MCTO/MCTO </sup></i>mice show developmental defects in body weight from postnatal day 0, which persist as they age. They also exhibit high urine albumin creatinine levels from a young age, mimicking the nephropathic symptoms of MCTO patients. Characteristics of glomerular sclerosis reported in human patients are also observed, such as histological evidence of focal segmental glomerulosclerosis (FSGS), podocyte foot process microvillus transformation and podocyte foot process effacement. Therefore, this study contributes to the development of an alternative treatment for MCTO nephropathy by providing a viable mouse model.</p>

収録刊行物

  • 実験動物彙報

    実験動物彙報, 2018

    公益社団法人 日本実験動物学会

各種コード

  • NII論文ID(NAID)
    130007501195
  • 本文言語コード
    ENG
  • ISSN
    1341-1357
  • データ提供元
    J-STAGE 
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