2015年10月
Oncogenic Lmo3 cooperates with Hen2 to induce hydrocephalus in mice
EXPERIMENTAL ANIMALS
- 巻
- 64
- 号
- 4
- 開始ページ
- 407
- 終了ページ
- 414
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1538/expanim.15-0026
- 出版者・発行元
- INT PRESS EDITING CENTRE INC
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.
- リンク情報
- ID情報
-
- DOI : 10.1538/expanim.15-0026
- ISSN : 1341-1357
- eISSN : 1881-7122
- PubMed ID : 26156403
- Web of Science ID : WOS:000364603000010