Neuron-Speciﬁc Menin Deletion Leads to Synaptic Dysfunction

AAV-p35 and AAV-GFP was used to test whether p35 expression could rescue synaptic deﬁcits and impaired learning and memory defects observed in CcKO mice. (From BrainVTA)

The viruses used in this article from BrainVTA are in the table below

Custom-Made AAVs	AAV2-CamKII-p35-T2A-GFP-WPRE
	AAV2-CamKII-T2A-GFP-WPRE

Kai Zhuang, Changquan Huang, Lige Leng, Honghua Zheng, Yuehong Gao, Guimiao Chen, Zhilin Ji, Hao Sun, Yu Hu, Di Wu, Meng Shi, Huifang Li, Yingjun Zhao, Yunwu Zhang, Maoqiang Xue, Guojun Bu, Timothy Y. Huang, Huaxi Xu and Jie Zhang
Pub Date: 2018-07-17, DOI: 10.1016/j.celrep.2018.06.055, Email: sales@brainvta.com

Menin (MEN1) is a critical modulator of tissue development and maintenance. As such, MEN1 mutations are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. Although menin is abundantly expressed in the nervous system, little is known with regard to its function in the adult brain. Here, we demonstrate that neuron-speciﬁc deletion of Men1 (CcKO) affects dendritic branching and spine formation, resulting in defects in synaptic function, learning, and memory. Furthermore, we ﬁnd that menin binds to the p35 promoter region to facilitate p35 transcription. As a primary Cdk5 activator, p35 is expressed mainly in neurons and is critical for brain development and synaptic plasticity. Restoration of p35 expression in the hippocampus and cortex of Men1 CcKO mice rescues synaptic and cognitive deﬁcits associated withMen1 deletion. These results reveal a critical role for menin in synaptic and cognitive function by modulating the p35-Cdk5 pathway.

Figure 1. Exogenous p35 Expression Rescues Cognitive Impairment and Synaptic Deﬁcits in CcKO Mice

The biological function of menin in neurons remains unclear. Zhuang et al. report that menin regulates neuronal dendritic branching, spine density, and synaptic plasticity. Menin binds to the p35 promoter to enhance p35 transcription and CDK5 activity. The study demonstrates a role for menin in synaptic and cognitive function.

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