Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice

Serine Incorporator 2(SERINC2), a highly conserved eukaryotic membrane lipid regulator, promotes critical membrane lipid biosynthesis to maintain neuronal metabolic homeostasis by assembling serine synthase complexes. Our team previously identified SERINC2 as a bipolar disorder (BD) risk gene in Chi...

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Main Authors: Tianlang Ke, Ruilan Yang, Zewen Tan, Liping Cao, Xuemei Liu
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025003314
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author Tianlang Ke
Ruilan Yang
Zewen Tan
Liping Cao
Xuemei Liu
author_facet Tianlang Ke
Ruilan Yang
Zewen Tan
Liping Cao
Xuemei Liu
author_sort Tianlang Ke
collection DOAJ
description Serine Incorporator 2(SERINC2), a highly conserved eukaryotic membrane lipid regulator, promotes critical membrane lipid biosynthesis to maintain neuronal metabolic homeostasis by assembling serine synthase complexes. Our team previously identified SERINC2 as a bipolar disorder (BD) risk gene in Chinese Han familial BD cases, with mutations affecting cerebral white matter volume. Despite established clinical relevance, brain expression patterns of SERINC2 remains poorly characterized experimentally. We used RNAscope® in situ hybridization to comprehensively map SERINC2 mRNA distribution across mouse coronal brain sections, and quantified positive cells across regions. Given BD's potential association with excitatory/inhibitory imbalance, multiplex fluorescence in situ hybridization examined SERINC2 co-expression patterns with vesicular glutamate transporter 2 (VGLUT2, marker for glutamatergic neurons) and glutamic acid decarboxylase 2 (GAD2, marker for GABAergic neurons) in SERINC2-positive regions. Widespread SERINC2 expression was observed in in the telencephalon and diencephalon, including cortical areas (neocortex and limbic cortex), hippocampal subregions (CA1 - CA3, dentate gyrus, and subiculum), thalamic nuclei, and basolateral amygdala. High-intensity signals were detected in hindbrain regions, particularly the pontine nuclei (PN) and reticulotegmental nucleus of the pons (RtTg). Cerebellar Purkinje and granular layers also exhibited significant expression. Notably, multiplex fluorescence in situ hybridization revealed SERINC2 + /VGLUT2 + co-expression in cortical layers III-IV, dorsal subiculum, thalamus, PN, and RtTg. Co-expression of SERINC2 + /GAD2 + was identified in the cerebellar Purkinje cell layer. These findings delineate the brain-wide expression landscape of SERINC2 in mice and provide a neuroanatomical basis for studying its role in excitation/inhibition imbalance in the pathogenesis of BD.
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spelling doaj-art-6a14029589be4bb4bf16d98e8e1e239d2025-08-25T04:13:58ZengElsevierBrain Research Bulletin1873-27472025-10-0123011151910.1016/j.brainresbull.2025.111519Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J miceTianlang Ke0Ruilan Yang1Zewen Tan2Liping Cao3Xuemei Liu4The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, ChinaThe Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, ChinaThe Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, ChinaThe Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China; Corresponding author at: The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China.CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen–Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Shenzhen Key Lab of Neuropsychiatric Modulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China; Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; Corresponding author at: CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen–Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.Serine Incorporator 2(SERINC2), a highly conserved eukaryotic membrane lipid regulator, promotes critical membrane lipid biosynthesis to maintain neuronal metabolic homeostasis by assembling serine synthase complexes. Our team previously identified SERINC2 as a bipolar disorder (BD) risk gene in Chinese Han familial BD cases, with mutations affecting cerebral white matter volume. Despite established clinical relevance, brain expression patterns of SERINC2 remains poorly characterized experimentally. We used RNAscope® in situ hybridization to comprehensively map SERINC2 mRNA distribution across mouse coronal brain sections, and quantified positive cells across regions. Given BD's potential association with excitatory/inhibitory imbalance, multiplex fluorescence in situ hybridization examined SERINC2 co-expression patterns with vesicular glutamate transporter 2 (VGLUT2, marker for glutamatergic neurons) and glutamic acid decarboxylase 2 (GAD2, marker for GABAergic neurons) in SERINC2-positive regions. Widespread SERINC2 expression was observed in in the telencephalon and diencephalon, including cortical areas (neocortex and limbic cortex), hippocampal subregions (CA1 - CA3, dentate gyrus, and subiculum), thalamic nuclei, and basolateral amygdala. High-intensity signals were detected in hindbrain regions, particularly the pontine nuclei (PN) and reticulotegmental nucleus of the pons (RtTg). Cerebellar Purkinje and granular layers also exhibited significant expression. Notably, multiplex fluorescence in situ hybridization revealed SERINC2 + /VGLUT2 + co-expression in cortical layers III-IV, dorsal subiculum, thalamus, PN, and RtTg. Co-expression of SERINC2 + /GAD2 + was identified in the cerebellar Purkinje cell layer. These findings delineate the brain-wide expression landscape of SERINC2 in mice and provide a neuroanatomical basis for studying its role in excitation/inhibition imbalance in the pathogenesis of BD.http://www.sciencedirect.com/science/article/pii/S0361923025003314Serine incorporator 2Bipolar disorderRNAscope
spellingShingle Tianlang Ke
Ruilan Yang
Zewen Tan
Liping Cao
Xuemei Liu
Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice
Brain Research Bulletin
Serine incorporator 2
Bipolar disorder
RNAscope
title Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice
title_full Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice
title_fullStr Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice
title_full_unstemmed Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice
title_short Whole-brain spatial distribution of serine incorporator 2 mRNA in adult C57BL/6 J mice
title_sort whole brain spatial distribution of serine incorporator 2 mrna in adult c57bl 6 j mice
topic Serine incorporator 2
Bipolar disorder
RNAscope
url http://www.sciencedirect.com/science/article/pii/S0361923025003314
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