Schizophrenia Patient Shows a Rare Interleukin 15 Receptor alpha Variant Disrupting Signal Transduction

Title:Schizophrenia Patient Shows a Rare Interleukin 15 Receptor alpha Variant Disrupting Signal Transduction

Volume: 19 Issue: 8

Author(s): Yanli Pan, Zhimin Wang, Guangping Zhang, Junhua Guo, Xuequan Zhu, Jia Zhou, Zhenrong Zhang, Zuoli Sun, Jian Yang, Abba J. Kastin, Weihong Pan, Xiaojun Wu, Jianliang Zhang, Xiaomin Wang, Chuanyue Wang and Yi He*

Affiliation:

• The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, 100088,China

Keywords: Interleukin 15 receptor alpha, interleukin 15, single nucleotide polymorphism, schizophrenia, IL-15RA, STAT3 phosphorylation.

Abstract:

Background: Schizophrenia is a complex and debilitating mental disorder with strong heritability. Its pathogenesis involves immune dysregulation. Interleukin 15 and interleukin 15 receptor alpha(IL-15Rα) are classical immune molecules. They also help maintain normal brain function, leading to our hypothesis that IL-15Rα gene(IL- 15RA) variants contribute to the pathogenesis of schizophrenia.

Objective: We determine whether the genetic variants of IL-15RA are associated with the development and progression of schizophrenia and whether IL-15RA single nucleotide polymorphism(SNP) plays a key role in downstream signaling transduction.

Methods and Results: We sequenced IL-15RA exon from 132 Chinese schizophrenic patients and identified a rare variant(rs528238821) in a patient diagnosed with catatonic schizophrenia and ankylosing spondylitis(AS). We overexpressed this missense variant in cells driven by pBI-CMV vector. The cells showed attenuated STAT3 phosphorylation in response to interleukin15.

Conclusion: IL-15RA mutation is rare in schizophrenic patients but interfered with IL- 15Rα intracellular signal transduction. Given the similarity of symptoms of catatonic schizophrenia and the known phenotype of IL-15Rα knockout mice, gene variation might offer diagnostic value for sub-types of schizophrenia.

Cite this article as:

Pan Yanli , Wang Zhimin , Zhang Guangping , Guo Junhua , Zhu Xuequan , Zhou Jia , Zhang Zhenrong, Sun Zuoli , Yang Jian , Kastin J. Abba , Pan Weihong , Wu Xiaojun , Zhang Jianliang , Wang Xiaomin , Wang Chuanyue and He Yi *, Schizophrenia Patient Shows a Rare Interleukin 15 Receptor alpha Variant Disrupting Signal Transduction, Current Molecular Medicine 2019; 19 (8) . https://dx.doi.org/10.2174/1566524019666190617172054