Evidence map›Paper›PMID 19361477›Full record

ArticleNeuroscience2009

Disturbances in the secretion of neurotransmitters in IA-2/IA-2beta null mice: changes in behavior, learning and lifespan.

T Nishimura, A Kubosaki, Y Ito, A L Notkins

Open access · greenAbstract read
In one paragraph

Article in Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.6field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 48 citations in OpenAlex.

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  7. Genetic Markers of Postmortem Brain Iron.Journal of neurochemistry · 2025
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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

4 authors at 2 institutions in 1 country.

T NishimuraExperimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4322, USA.
A Kubosaki
Y Ito
A L Notkins
National Institute of Dental and Craniofacial Research · USNational Institutes of Health · US

Funding

Insulin-Dependent Diabetes MellitusZIADE000423 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI NOTKINS, ABNER L. · 2009 to 2020
$16.9M
INSULIN-DEPENDENT DIABETES MELLITUSZ01DE000423 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI NOTKINS, ABNER L. · 1986 to 2008
$3.5M
Vortex Countercurrent ChromatographyZIAHL001060 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ITO, YOICHIRO · 2009 to 2012
$866k
Intramural NIH HHS Z01 DE000423Intramural NIH HHS Z99 DE999999
6 · The paper itself

Abstract

Islet-associated protein 2 (IA-2) and IA-2beta are major autoantigens in type 1 diabetes and transmembrane proteins in dense core secretory vesicles (DCV) of neuroendocrine cells. The deletion of these genes results in a decrease in insulin secretion. The present study was initiated to test the hypothesis that this deletion not only affects the secretion of insulin, but has a more global effect on neuroendocrine secretion that leads to disturbances in behavior and learning. Measurement of neurotransmitters showed that norepinephrine, dopamine and 5-HT were significantly decreased in the brain of double knockout (DKO) mice (P<0.05 to <0.001). In tests evaluating anxiety-like behavior and conditioned-learning, the DKO mice showed a highly significant increase in anxiety-like behavior (P<0.01 to <0.001) and impairment of conditioned learning (P<0.01) as compared to WT mice. The DKO mice also displayed an increase in spontaneous and induced seizures (P<0.01) and age-related death. Contrary to the generally held view that IA-2 and IA-2beta are expressed exclusively in DCV, subcellular fractionation studies revealed that IA-2beta, but not IA-2, co-purifies with fractions rich in synaptic vesicles (SV), and that the secretion of dopamine, GABA and glutamate from the synaptosomes of the DKO mice was significantly decreased as was the number of SV (P<0.01). Taken together, these findings show that IA-2beta is present in both DCV and SV, and that the deletion of IA-2/IA-2beta has a global effect on the secretion of neurotransmitters. The impairment of secretion leads to behavioral and learning disturbances, seizures and reduced lifespan.

Indexed as

Age FactorsAnimalsAntidepressive Agents, Second-GenerationBehavior, AnimalBiotinylationBrainCells, CulturedConditioning, PsychologicalDrinkingExploratory BehaviorFemaleHindlimb SuspensionInsulinInsulin SecretionMaleMiceAntidepressive Agents, Second-GenerationInsulinNeurotransmitter AgentsPentylenetetrazoleProtein Tyrosine Phosphatase, Non-Receptor Type 1Ptpn1 protein, mousePtprn protein, mouseReceptor-Like Protein Tyrosine Phosphatases, Class 8Synapsins

Identifiers

PMID19361477
PMCPMC2672562
OpenAlexW2027937356

What OpenQuestion holds

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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.