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The Protein Dendrite Arborization and Synapse Maturation 1 (Dasm-1) Is Dispensable for Dendrite Arborization

机译:蛋白质树突乔木和突触成熟1(Dasm-1)是不必要的树突乔木。

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摘要

The development of a highly branched dendritic tree is essential for the establishment of functional neuronal connections. The evolutionarily conserved immunoglobulin superfamily member, the protein dendrite arborization and synapse maturation 1 (Dasm-1) is thought to play a critical role in dendrite formation of dissociated hippocampal neurons. RNA interference-mediated Dasm-1 knockdown was previously shown to impair dendrite, but not axonal, outgrowth and branching (S. H. Shi, D. N. Cox, D. Wang, L. Y. Jan, and Y. N. Jan, Proc. Natl. Acad. Sci. USA 101:13341-13345, 2004). Here, we report the generation and analysis of Dasm-1 null mice. We find that genetic ablation of Dasm-1 does not interfere with hippocampal dendrite growth and branching in vitro and in vivo. Moreover, the absence of Dasm-1 does not affect the modulation of dendritic outgrowth induced by brain-derived neurotrophic factor. Importantly, the previously observed impairment in dendrite growth after Dasm-1 knockdown is also observed when the Dasm-1 knockdown is performed in cultured hippocampal neurons from Dasm-1 null mice. These findings indicate that the dendrite arborization phenotype was caused by off-target effects and that Dasm-1 is dispensable for hippocampal dendrite arborization.
机译:建立高度分支的树状树对于建立功能性神经元连接至关重要。进化上保守的免疫球蛋白超家族成员,蛋白质树突状树突触和突触成熟1(Dasm-1)被认为在离体海马神经元的树突状形成中起关键作用。 RNA干扰介导的Dasm-1敲低以前被证明会损害树突,但不损害轴突,生长和分支(SH Shi,DN Cox,D。Wang,LY Jan和YN Jan,美国国家科学院学报101 :13341-13345,2004)。在这里,我们报告Dasm-1空小鼠的生成和分析。我们发现,Dasm-1的遗传消融在体外和体内均不干扰海马树突的生长和分支。而且,Dasm-1的缺失不会影响脑源性神经营养因子诱导的树突生长的调节。重要的是,在从Dasm-1缺失小鼠培养的海马神经元中进行Dasm-1敲除时,也观察到了Dasm-1敲除后树突生长的先前损害。这些发现表明,树突状乔木表型是由脱靶效应引起的,Dasm-1对于海马树突状乔木化是必不可少的。

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