RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus

Ming Yi Chou; Meng Chuen Hu; Pin Yu Chen; Chi Lin Hsu; Ting Yu Lin; Mao Jia Tan; Chih Yu Lee; Meng Fai Kuo; Pei Hsin Huang; Vin Cent Wu; Shih Hung Yang; Pi Chuan Fan; Hsin Yi Huang; Schahram Akbarian; Tsui Han Loo; Colin L. Stewart; Hsiang Po Huang; Susan Shur Fen Gau; Hsien Sung Huang

doi:10.1093/hmg/ddac110

RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus

Ming Yi Chou, Meng Chuen Hu, Pin Yu Chen, Chi Lin Hsu, Ting Yu Lin, Mao Jia Tan, Chih Yu Lee, Meng Fai Kuo, Pei Hsin Huang, Vin Cent Wu, Shih Hung Yang, Pi Chuan Fan, Hsin Yi Huang, Schahram Akbarian, Tsui Han Loo, Colin L. Stewart, Hsiang Po Huang, Susan Shur Fen Gau, Hsien Sung Huang

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13 Scopus citations

Abstract

RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.

Original language	English
Pages (from-to)	3161-3180
Number of pages	20
Journal	Human Molecular Genetics
Volume	31
Issue number	18
DOIs	https://doi.org/10.1093/hmg/ddac110
State	Published - 15 Sep 2022

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Chou, M. Y., Hu, M. C., Chen, P. Y., Hsu, C. L., Lin, T. Y., Tan, M. J., Lee, C. Y., Kuo, M. F., Huang, P. H., Wu, V. C., Yang, S. H., Fan, P. C., Huang, H. Y., Akbarian, S., Loo, T. H., Stewart, C. L., Huang, H. P., Gau, S. S. F., & Huang, H. S. (2022). RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus. Human Molecular Genetics, 31(18), 3161-3180. https://doi.org/10.1093/hmg/ddac110

@article{b4a2def28ff9400c9b0f25b5ba0f57c2,

title = "RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus",

abstract = "RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.",

author = "Chou, {Ming Yi} and Hu, {Meng Chuen} and Chen, {Pin Yu} and Hsu, {Chi Lin} and Lin, {Ting Yu} and Tan, {Mao Jia} and Lee, {Chih Yu} and Kuo, {Meng Fai} and Huang, {Pei Hsin} and Wu, {Vin Cent} and Yang, {Shih Hung} and Fan, {Pi Chuan} and Huang, {Hsin Yi} and Schahram Akbarian and Loo, {Tsui Han} and Stewart, {Colin L.} and Huang, {Hsiang Po} and Gau, {Susan Shur Fen} and Huang, {Hsien Sung}",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Oxford University Press.",

year = "2022",

month = sep,

day = "15",

doi = "10.1093/hmg/ddac110",

language = "English",

volume = "31",

pages = "3161--3180",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "18",

}

Chou, MY, Hu, MC, Chen, PY, Hsu, CL, Lin, TY, Tan, MJ, Lee, CY, Kuo, MF, Huang, PH, Wu, VC, Yang, SH, Fan, PC, Huang, HY, Akbarian, S, Loo, TH, Stewart, CL, Huang, HP, Gau, SSF & Huang, HS 2022, 'RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus', Human Molecular Genetics, vol. 31, no. 18, pp. 3161-3180. https://doi.org/10.1093/hmg/ddac110

TY - JOUR

T1 - RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus

AU - Chou, Ming Yi

AU - Hu, Meng Chuen

AU - Chen, Pin Yu

AU - Hsu, Chi Lin

AU - Lin, Ting Yu

AU - Tan, Mao Jia

AU - Lee, Chih Yu

AU - Kuo, Meng Fai

AU - Huang, Pei Hsin

AU - Wu, Vin Cent

AU - Yang, Shih Hung

AU - Fan, Pi Chuan

AU - Huang, Hsin Yi

AU - Akbarian, Schahram

AU - Loo, Tsui Han

AU - Stewart, Colin L.

AU - Huang, Hsiang Po

AU - Gau, Susan Shur Fen

AU - Huang, Hsien Sung

PY - 2022/9/15

Y1 - 2022/9/15

N2 - RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.

AB - RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.

UR - http://www.scopus.com/inward/record.url?scp=85138447029&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddac110

DO - 10.1093/hmg/ddac110

M3 - Article

C2 - 35567414

AN - SCOPUS:85138447029

SN - 0964-6906

VL - 31

SP - 3161

EP - 3180

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 18

ER -

RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus

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