Oncogenic <i>Lmo3</i> cooperates with <i>Hen2</i> to induce hydrocephalus in mice

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Author(s)

    • ISOGAI Eriko Isogai Eriko
    • Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan
    • OKUMURA Kazuhiro Fushiki Shinji
    • Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
    • Wakabayashi Yuichi
    • Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan
    • Okumura Kazuhiro
    • Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan
    • Saito Megumi
    • Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan
    • Yoshizawa Yasuhiro
    • Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan
    • Itoh Kyoko
    • Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
    • Tando So
    • Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
    • Ohira Miki
    • Lababoratory of Cancer Genomics, Chiba Cancer Center Research Institute, Japan
    • Haraguchi Seiki
    • Lababoratory of Embryonic, Genetic Engineering, Chiba Cancer Center Research Institute, Japan|Breeding and Reproduction Research, Division of Animal Reproduction Research Group, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization, 2 Ikenodai, Tsukuba, Ibaraki 305-0901, Japan
    • Nakagawara Akira
    • Division of Biochemistry, Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Japan

Abstract

We previously reported that LMO3 and HEN2 act as oncogenes in neuroblastoma development through up-regulating <i>MASH1</i> transcription by interfering with HES1. To confirm these results <i>in vivo</i>, we generated transgenic mice of these genes. <i>Lmo3</i> or <i>Hen2</i> was expressed under the control of <i>Wnt1</i> promoter, which is expressed in the central nervous system and neural crest of the sympathoadrenal lineage from which neuroblastoma develops. Heterozygous <i>Lmo3</i> and <i>Hen2</i> transgenic mice (<i>Tg (Lmo3)</i> and <i>Tg (Hen2)</i>) developed hydrocephalus at higher frequency than for the wild type mice, and all heterozygous double-transgenic mice (<i>Tg (Lmo3</i>; <i>Hen2)</i>) developed hydrocephalus. Therefore, <i>Lmo3</i> and <i>Hen2</i> may be involved in and have synergistic effects on hydrocephalus development. Although aqueduct stenosis occurred in all genotypes, it was mild in <i>Tg (Lmo3</i>; <i>Hen2)</i> mice. Furthermore, hydrocephalus was detected at E18.5 in <i>Tg (Lmo3</i>; <i>Hen2)</i>. These results suggest that the causes of hydrocephalus are not only aqueduct stenosis but also disorder of neocortical development. A similar phenotype was reported in <i>Robo1/2<sup>−/−</sup></i> mice, in which <i>Hes1</i> expression level was decreased in ventricular zone progenitors. Thus, it is suggested that the expression levels of <i>Lmo3</i> and/or <i>Hen2</i> could determine the fate of stem cells by inhibiting <i>Hes1</i> function during nervous system development and might be a trigger of aberrant neurogenesis <i>in vivo</i>.

Journal

  • Experimental Animals

    Experimental Animals 64(4), 407-414, 2015

    Japanese Association for Laboratory Animal Science

Codes

  • NII Article ID (NAID)
    130005104844
  • NII NACSIS-CAT ID (NCID)
    AA11032321
  • Text Lang
    ENG
  • ISSN
    1341-1357
  • NDL Article ID
    026817719
  • NDL Call No.
    Z54-H752
  • Data Source
    NDL  J-STAGE 
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