Evidence map›Paper›PMID 34785571›Full record

ArticleeNeuro

Off-Target Expression of Cre-Dependent Adeno-Associated Viruses in Wild-Type C57BL/6J Mice.

Justin J Botterill, Abdessattar Khlaifia, Brandon J Walters, Mark A Brimble, Helen E Scharfman, Maithe Arruda-Carvalho

Abstract read
In one paragraph

Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

31 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Neural circuits of torpor.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. AAV-PHP.eB Peripheral Delivery and Central Expression in Cre Mice.The Journal of comparative neurology · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
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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

6 authors.

Justin J BotterillDepartment of Psychology, University of Toronto Scarborough, Toronto, Ontario M1C 1A4, Canada.ORCID 0000-0002-3141-2281
Abdessattar KhlaifiaDepartment of Psychology, University of Toronto Scarborough, Toronto, Ontario M1C 1A4, Canada.
Brandon J WaltersDepartment of Cell & Systems Biology, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada.
Mark A BrimbleDepartment of Surgery, St. Jude Children's Research Hospital, Memphis, Tennnessee 38105.ORCID 0000-0001-7182-9818
Helen E ScharfmanCenter for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962.
Maithe Arruda-CarvalhoDepartment of Psychology, University of Toronto Scarborough, Toronto, Ontario M1C 1A4, Canada m.arrudacarvalho@utoronto.ca.ORCID 0000-0002-7832-3729

Funding

Hilar mossy cells and dentate gyrus functionR01MH109305 · NIMH · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI SCHARFMAN, HELEN E · 2016 to 2020
$2.0M
NIMH NIH HHS R01 MH109305
6 · The paper itself

Abstract

Adeno-associated viruses (AAVs) are a commonly used tool in neuroscience to efficiently label, trace, and/or manipulate neuronal populations. Highly specific targeting can be achieved through recombinase-dependent AAVs in combination with transgenic rodent lines that express Cre-recombinase in specific cell types. Visualization of viral expression is typically achieved through fluorescent reporter proteins (e.g., GFP or mCherry) packaged within the AAV genome. Although nonamplified fluorescence is usually sufficient to observe viral expression, immunohistochemical amplification of the fluorescent reporter is routinely used to improve viral visualization. In the present study, Cre-dependent AAVs were injected into the neocortex of wild-type C57BL/6J mice. While we observed weak but consistent nonamplified off-target double inverted open reading frame (DIO) expression in C57BL/6J mice, antibody amplification of the GFP or mCherry reporter revealed notable Cre-independent viral expression. Off-target expression of DIO constructs in wild-type C57BL/6J mice occurred independent of vendor, AAV serotype, or promoter. We also evaluated whether Cre-independent expression had functional effects via designer receptors exclusively activated by designer drugs (DREADDs). The DREADD agonist C21 (compound 21) had no effect on contextual fear conditioning or c-Fos expression in DIO-hM3Dq-mCherry

Indexed as

DependovirusIntegrasesAnimalsImidazolesMiceMice, Inbred C57BLMice, TransgenicSulfonamidesThiophenescompound 21Cre recombinaseImidazolesIntegrasesSulfonamidesThiophenesantibody amplificationc-FosCre/loxPdouble inverted open reading frameDREADDsfear conditioningImmunofluorescence

Identifiers

PMID34785571
PMCPMC8614227

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.