File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Lrrc7 mutant mice model developmental emotional dysregulation that can be alleviated by mGluR5 allosteric modulation

TitleLrrc7 mutant mice model developmental emotional dysregulation that can be alleviated by mGluR5 allosteric modulation
Authors
Keywordsaggression
allosterism
animal cell
animal experiment
animal model
Issue Date2019
PublisherNature Publishing Group: Open Access Journals - Option B. The Journal's web site is located at http://www.nature.com/tp/index.html
Citation
Translational Psychiatry, 2019, v. 9, p. article no. 244 How to Cite?
AbstractLRRC7 has been identified as a candidate gene for severe childhood emotional dysregulation. Direct experimental evidence for a role of LRRC7 in the disease is needed, as is a better understanding of its impact on neuronal structure and signaling, and hence potential treatment targets. Here, we generated and analyzed an Lrrc7 mutant mouse line. Consistent with a critical role of LRRC7 in emotional regulation, mutant mice had inappropriate juvenile aggressive behavior and significant anxiety-like behavior and social dysfunction in adulthood. The pivotal role of mGluR5 signaling was demonstrated by rescue of behavioral defects with augmentation of mGluR5 receptor activity by 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB). Intra-peritoneal injection of CDPPB alleviated abnormal juvenile behavior, as well as anxiety-like behavior and hypersociability at adulthood. Furthermore, mutant primary neurons had impaired neurite outgrowth which was rescued by CDPPB treatment. In conclusion, Lrrc7 mutant mice provide a valuable tool to model childhood emotional dysregulation and persistent mental health comorbidities. Moreover, our data highlight an important role of LRRC7 in mGluR5 signaling, which is a potential new treatment target for anxiety and social dysfunction.
Persistent Identifierhttp://hdl.handle.net/10722/279192
ISSN
2023 Impact Factor: 5.8
2023 SCImago Journal Rankings: 2.203
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChong, CH-
dc.contributor.authorLi, Q-
dc.contributor.authorMak, PHS-
dc.contributor.authorNg, CCP-
dc.contributor.authorLEUNG, EHW-
dc.contributor.authorTAN, VH-
dc.contributor.authorChan, AKW-
dc.contributor.authorMcAlonan, G-
dc.contributor.authorChan, SY-
dc.date.accessioned2019-10-21T02:21:18Z-
dc.date.available2019-10-21T02:21:18Z-
dc.date.issued2019-
dc.identifier.citationTranslational Psychiatry, 2019, v. 9, p. article no. 244-
dc.identifier.issn2158-3188-
dc.identifier.urihttp://hdl.handle.net/10722/279192-
dc.description.abstractLRRC7 has been identified as a candidate gene for severe childhood emotional dysregulation. Direct experimental evidence for a role of LRRC7 in the disease is needed, as is a better understanding of its impact on neuronal structure and signaling, and hence potential treatment targets. Here, we generated and analyzed an Lrrc7 mutant mouse line. Consistent with a critical role of LRRC7 in emotional regulation, mutant mice had inappropriate juvenile aggressive behavior and significant anxiety-like behavior and social dysfunction in adulthood. The pivotal role of mGluR5 signaling was demonstrated by rescue of behavioral defects with augmentation of mGluR5 receptor activity by 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB). Intra-peritoneal injection of CDPPB alleviated abnormal juvenile behavior, as well as anxiety-like behavior and hypersociability at adulthood. Furthermore, mutant primary neurons had impaired neurite outgrowth which was rescued by CDPPB treatment. In conclusion, Lrrc7 mutant mice provide a valuable tool to model childhood emotional dysregulation and persistent mental health comorbidities. Moreover, our data highlight an important role of LRRC7 in mGluR5 signaling, which is a potential new treatment target for anxiety and social dysfunction.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals - Option B. The Journal's web site is located at http://www.nature.com/tp/index.html-
dc.relation.ispartofTranslational Psychiatry-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectaggression-
dc.subjectallosterism-
dc.subjectanimal cell-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.titleLrrc7 mutant mice model developmental emotional dysregulation that can be alleviated by mGluR5 allosteric modulation-
dc.typeArticle-
dc.identifier.emailLi, Q: liqi@hkucc.hku.hk-
dc.identifier.emailMak, PHS: hsmak@hkucc.hku.hk-
dc.identifier.emailChan, SY: sychan@hkucc.hku.hk-
dc.identifier.authorityChan, SY=rp00356-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41398-019-0580-9-
dc.identifier.pmid31582721-
dc.identifier.pmcidPMC6776540-
dc.identifier.scopuseid_2-s2.0-85072926396-
dc.identifier.hkuros307262-
dc.identifier.volume9-
dc.identifier.spagearticle no. 244-
dc.identifier.epagearticle no. 244-
dc.identifier.isiWOS:000489967900004-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2158-3188-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats