Schizophrenia Patient Shows a Rare Interleukin 15 Receptor alpha Variant Disrupting Signal Transduction
| Autor: | Jianliang Zhang, Zhenrong Zhang, Jia Zhou, Xuequan Zhu, Xiaojun Wu, Zuoli Sun, Xiaomin Wang, Jian Yang, Yi He, Weihong Pan, Yanli Pan, Junhua Guo, Abba J. Kastin, Chuanyue Wang, Zhimin Wang, Guangping Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
STAT3 Transcription Factor 0301 basic medicine Mutation Missense Single-nucleotide polymorphism medicine.disease_cause Polymorphism Single Nucleotide Biochemistry 03 medical and health sciences 0302 clinical medicine Asian People Interleukin-15 Receptor alpha Subunit Loss of Function Mutation Animals Humans Point Mutation Missense mutation Medicine Spondylitis Ankylosing Phosphorylation Molecular Biology Interleukin-15 Mice Knockout Schizophrenia Paranoid Schizophrenia Catatonic business.industry Exons General Medicine Middle Aged Immune dysregulation Recombinant Proteins Pedigree Intracellular signal transduction Interleukin-15 receptor HEK293 Cells 030104 developmental biology Amino Acid Substitution Interleukin 15 Immunology Knockout mouse Molecular Medicine Signal transduction business Protein Processing Post-Translational 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Current Molecular Medicine. 19:560-569 |
| ISSN: | 1566-5240 |
| DOI: | 10.2174/1566524019666190617172054 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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