What do we learn from the murine Jacob/Nsmf gene knockout for human disease?
What do we learn from the murine Jacob/Nsmf gene knockout for human disease?
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DOI：
10.1080/21675511.2016.1241361
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Kreutz MR
中科院分区：
文献类型：
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作者：
Spilker C;Grochowska KM;Kreutz MR
NSMF基因的突变与卡尔曼综合征有关。关于由NSMF基因编码的蛋白Jacob/NELF的亚细胞定位，报道了相互矛盾的结果。一些报道指出GnRH阳性神经元的细胞外定位和作为引导分子的功能，使其从嗅觉胎盘迁移到下丘脑。其他研究表明雅各布的蛋白质从突触到细胞核的运输，并表明该蛋白质在神经元活动依赖的基因表达中发挥了作用。最近的一篇文章对Jacob/NELF在Kallmann综合征中的主要作用以及GnRH阳性神经元在早期发育过程中的神经元迁移提出了质疑。相反，小鼠NSMF基因敲除会导致海马区发育不良，树突形成过程中BDNF信号受损，以及与出生后早期缺乏BDNF诱导的Jacob核输入相关的表型。
Mutations in the NSMF gene have been related to Kallmann syndrome. Conflicting results have been reported on the subcellular localization of Jacob/NELF, the protein encoded by the NSMF gene. Some reports indicate an extracellular localization and a function as a guidance molecule for migration of GnRH-positive neurons from the olfactory placode to the hypothalamus. Other studies have shown protein transport of Jacob from synapse-to-nucleus and indicate a role of the protein in neuronal activity-dependent gene expression. A recent publication casts doubts on a major role of Jacob/NELF in Kallmann syndrome and neuronal migration of GnRH-positive neurons during early development. Instead a murine NSMF gene knockout results in hippocampal dysplasia, impaired BDNF-signaling during dendritogenesis, and phenotypes related to the lack of BDNF-induced nuclear import of Jacob in early postnatal development.