Oncogenic <i>Lmo3</i> cooperates with <i>Hen2</i> to induce hydrocephalus in mice
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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>.
- Experimental Animals
Experimental Animals 64(4), 407-414, 2015
Japanese Association for Laboratory Animal Science