Evidence map›Paper›PMID 31476380›Full record

ArticleNeurobiology of disease2019

Purkinje cell-specific Grip1/2 knockout mice show increased repetitive self-grooming and enhanced mGluR5 signaling in cerebellum.

Rebeca Mejias, Shu-Ling Chiu, Mei Han, Rebecca Rose, Ana Gil-Infante, Yifan Zhao, Richard L Huganir, Tao Wang

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
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  3. Neural substrates for regulating self-grooming behavior in rodents.Journal of Zhejiang University. Science. B · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Rebeca MejiasMcKusick-Nathans Department of Genetic Medicine and Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Physiology, University of Seville, 41012 Seville, Spain. Electronic address: rmejias@us.es.
Shu-Ling ChiuDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
Mei HanMcKusick-Nathans Department of Genetic Medicine and Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA.
Rebecca RoseMcKusick-Nathans Department of Genetic Medicine and Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA.
Ana Gil-InfanteDepartment of Physiology, University of Seville, 41012 Seville, Spain.
Yifan ZhaoMcKusick-Nathans Department of Genetic Medicine and Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA.
Richard L HuganirDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
Tao WangMcKusick-Nathans Department of Genetic Medicine and Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: twang9@jhmi.edu.
Johns Hopkins University · USUniversidad de Sevilla · ES

Funding

PDZ DOMAINS AND EXCITATORY SYNAPTIC FUNCTIONR01NS036715 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 1997 to 2020
$8.6M
AMPA receptor trafficking regulates social behaviors in autismR01MH112808 · NIMH · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L, WANG, TAO · 2017 to 2021
$2.0M
DHHC 15 palmitoylation modulates striatal dopamine systemR21NS085358 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, TAO · 2014 to 2015
$446k
NIMH NIH HHS R01 MH112808NINDS NIH HHS R01 NS036715NINDS NIH HHS R21 NS085358
6 · The paper itself

Abstract

Cerebellar Purkinje cell (PC) loss is a consistent pathological finding in autism. However, neural mechanisms of PC-dysfunction in autism remain poorly characterized. Glutamate receptor interacting proteins 1/2 (Grip1/2) regulate AMPA receptor (AMPAR) trafficking and synaptic strength. To evaluate role of PC-AMPAR signaling in autism, we produced PC-specific Grip1/2 knockout mice by crossing Grip2 conventional and Grip1 conditional KO with L7-Cre driver mice. PCs in the mutant mice showed normal morphology and number, and a lack of Grip1/2 expression. Rodent behavioral testing identified normal ambulation, anxiety, social interaction, and an increase in repetitive self-grooming. Electrophysiology studies revealed normal mEPSCs but an impaired mGluR-LTD at the Parallel Fiber-PC synapses. Immunoblots showed increased expression of mGluR5 and Arc, and enhanced phosphorylation of P38 and AKT in cerebellum of PC-specific Grip1/2 knockout mice. Results indicate that loss of Grip1/2 in PCs contributes to increased repetitive self-grooming, a core autism behavior in mice. Results support a role of AMPAR trafficking defects in PCs and disturbances of mGluR5 signaling in cerebellum in the pathogenesis of repetitive behaviors.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAutistic DisorderExcitatory Postsynaptic PotentialsGroomingIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNerve Tissue ProteinsProtein TransportPurkinje CellsReceptor, Metabotropic Glutamate 5Receptors, AMPASignal TransductionAdaptor Proteins, Signal TransducingGrip1 protein, mouseGrip2 protein, mouseGrm5 protein, mouseIntracellular Signaling Peptides and ProteinsNerve Tissue ProteinsReceptor, Metabotropic Glutamate 5Receptors, AMPAAMPA receptorsAutismCerebellumGlutamate signalingGrip1/2GroomingLTDmGluR receptorsPurkinje cells

Identifiers

PMID31476380
PMCPMC6939616
OpenAlexW2971070126

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.