Identification, characterization and expression profiles of PSEN2 in the Chinese tree shrew (Tupaia belangeri chinensis).

Ming Xue Li ,Xiao Mei Sun ,Wen Guang Wang ,Dexuan Kuang ,Lei Ruan ,Xin Huang,Xiao Hui Li ,Jie Dai ,Cai Xia Lu

doi:10.31083/j.jin.2020.02.28

Abstract

The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase. Mutations in PSEN2 are not only related to Alzheimer's disease but are also involved in other diseases. The Chinese tree shrew (Tupaia belangeri chinensis) is a potential animal model for Alzheimer's disease, although little is known about its cDNA sequence, protein structure, and PSEN2 expression. To better understand PSEN2 in the tree shrew, we cloned this gene by rapid amplification of cDNA ends technology. Hence, we analyzed the sequence and molecular characteristics of PSEN2 mRNA, predicted its spatial structure, and analyzed its expression profiles. We found that tree shrew PSEN2 is 1539 base pairs in length and encodes 330 amino acids. It is homologous and genetically similar to humans (97.64% identity). The protein structure of tree shrew PSEN2 indicated similarities to human PSEN2, both being comprised of numerous transmembrane helices. However, tree shrew PSEN2 possesses seven α-helices, and thus lacks three compared with human PSEN2. Tree shrew PSEN2 mRNAs were ubiquitously detected in all tissues, with a tissue- and temporal-specific pattern. These results pave the way towards the function of tree shrew PSEN2, which will give insights into the mechanisms leading to neurodegenerative and other diseases in humans.

Highlights

Presenilin 2 (PSEN2) is one of the significant components of γ-secretase (Wakabayashi and De Strooper, 2008)
3.1 Identification, cDNA cloning and homologous analyses of tree shrew PSEN2 (tsPSEN2) We identified the full length of tsPSEN2 cDNA in the brain of three individual specimens of the adult tree shrew group
3.2 Phylogenetic analysis of tsPSEN2 To gain an insight into the evolutionary relationship between the tree shrew and other species, a phylogenetic tree was constructed using the Neighbor-Joining (NJ) method, based on the PSEN2 protein sequences using the genetic database from GenBank

Summary

Introduction

Presenilin 2 (PSEN2) is one of the significant components of γ-secretase (as well as Presenilin 1, Nicastrin, and Aph-1) (Wakabayashi and De Strooper, 2008). It is encoded by the PSEN2 gene, localized to chromosome lq in humans (Levy-Lahad et al, 1995; Sherrington et al, 1995). Previous research has shown that missense mutations in PSEN2 are a rare cause of earlyonset Alzheimer's disease (AD) (www.alzforum.org/mutatio ns). It has previously been demonstrated that mutation of the PSEN2 does not damage the enzymatic function of γ-secretase but changes its digestion site leading to the production of aggregative Aβ (Uemura et al, 2009)

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Results

Conclusion