What do we learn from the murine Jacob/Nsmf gene knockout for human disease?

ABSTRACT

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.

KEYWORDS:

• BDNF
• CREB
• hippocampus
• Jacob
• Kallmann syndrome
• NELF
• synapse-to-nucleus

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Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

Supported by grants from the Deutsche Forschungsgemeinschaft (DFG Kr1879 / 5–1, 6–1; SFB779 TPB8), WGL Pakt f. Forschung, JPND (STAD), BMBF EnergI and People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7/2007-2013/ under REA grant agreement n [289581] NPlast to MRK.