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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2015 > Volume 64 Number 4 > Eriko Isogai1), Kazuhiro Okumura1), Megumi Saito1), Yasuhiro Yoshizawa1), Kyoko Itoh6), So Tando6), Miki Ohira2), Seiki Haraguchi3, 5), Akira Nakagawara4), Shinji Fushiki6), Hiroki Nagase7), and Yuichi Wakabayashi1)

Oncogenic Lmo3 cooperates with Hen2 to induce hydrocephalus in mice

Eriko Isogai1), Kazuhiro Okumura1), Megumi Saito1), Yasuhiro Yoshizawa1), Kyoko Itoh6), So Tando6), Miki Ohira2), Seiki Haraguchi3, 5), Akira Nakagawara4), Shinji Fushiki6), Hiroki Nagase7), and Yuichi Wakabayashi1)
1)Division of Experimental Animal Research, Chiba Cancer Center Research Institute, 666-2 Nitonacho, Chuouku, Chiba 260-8717, Japan 2)Lababoratory of Cancer Genomics, Chiba Cancer Center Research Institute, Japan 3)Lababoratory of Embryonic, Genetic Engineering, Chiba Cancer Center Research Institute, Japan 4)Division of Biochemistry, Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Japan 5)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 6)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 7)Division of Cancer Genetics, Chiba Cancer Center Research Institute, Japan
Abstract :

We previously reported that LMO3 and HEN2 act as oncogenes in neuroblastoma development through up-regulating MASH1 transcription by interfering with HES1. To confirm these results in vivo, we generated transgenic mice of these genes. Lmo3 or Hen2 was expressed under the control of Wnt1 promoter, which is expressed in the central nervous system and neural crest of the sympathoadrenal lineage from which neuroblastoma develops. Heterozygous Lmo3 and Hen2 transgenic mice (Tg (Lmo3) and Tg (Hen2)) developed hydrocephalus at higher frequency than for the wild type mice, and all heterozygous double-transgenic mice (Tg (Lmo3; Hen2)) developed hydrocephalus. Therefore, Lmo3 and Hen2 may be involved in and have synergistic effects on hydrocephalus development. Although aqueduct stenosis occurred in all genotypes, it was mild in Tg (Lmo3; Hen2) mice. Furthermore, hydrocephalus was detected at E18.5 in Tg (Lmo3; Hen2). 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 Robo1/2−/− mice, in which Hes1 expression level was decreased in ventricular zone progenitors. Thus, it is suggested that the expression levels of Lmo3 and/or Hen2 could determine the fate of stem cells by inhibiting Hes1 function during nervous system development and might be a trigger of aberrant neurogenesis in vivo.

Keywords :
hydrocephalus, neuroblastoma, neuronal development

Date Deposited : 07 Jan 2016 11:27

Last Modified : 07 Jan 2016 11:27

Official URL: http://https://www.jstage.jst.go.jp/browse/expanim/64/4/_contents

Volume 64, Number 4, July 2015 , ISSN 407–414

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