Evidence map›Paper›PMID 22974474›Full record

ArticleJournal of translational medicine2012

Development of a new humanized mouse model to study acute inflammatory arthritis.

Alexander V Misharin, G Kenneth Haines, Shawn Rose, Angelical K Gierut, Richard S Hotchkiss, Harris Perlman

Abstract read
In one paragraph

Article in Journal of translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–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

20 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Anti-inflammatory Activity of MTL-CEBPA, a Small Activating RNA Drug, in LPS-Stimulated Monocytes and Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  9. Review
  10. Humanized Mouse Models of Clinical Disease.Annual review of pathology · 2017
    Review
  11. Article
  12. Article
  13. Mice engrafted with human hematopoietic stem cells support a human myeloid cell inflammatory response in vivo.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2016
    Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Humanizing the mouse: in defense of murine models of critical illness.American journal of respiratory and critical care medicine · 2013
    Article
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.

Alexander V MisharinDepartment of Medicine/Rheumatology, Northwestern University, Feinberg School of Medicine, 240 East Huron Street, Room Chicago, IL 60611, USA.
G Kenneth Haines
Shawn Rose
Angelical K Gierut
Richard S Hotchkiss
Harris Perlman

Funding

Small Animal Surgery and HistologyP01HL108795 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LOSORDO, DOUGLAS W · 2011 to 2015
$10.7M
Prevention of Apoptotic Cell Death in Sepsis by BCL-2R37GM044118 · NIGMS · WASHINGTON UNIVERSITY · PI HOTCHKISS, RICHARD SAMUEL · 2003 to 2012
$5.1M
CELLULAR MECHANISMS OF SEPSIS AND ORGAN FAILURER01GM055194 · NIGMS · WASHINGTON UNIVERSITY · PI HOTCHKISS, RICHARD SAMUEL · 1997 to 2012
$4.7M
POSTDOCTORAL RHEUMATOLOGY TRAININGT32AR007611 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PERLMAN, HARRIS R · 2001 to 2022
$4.4M
Therapeutic Role for P21 in Suppressing IL-1 Beta Mediated PathologiesR01AR050250 · NIAMS · SAINT LOUIS UNIVERSITY · PI PERLMAN, HARRIS R · 2003 to 2014
$3.0M
PREVENTION OF APOPTOTIC CELL DEATH IN SEPSIS BY BCL-2R01GM044118 · NIGMS · WASHINGTON UNIVERSITY · PI HOTCHKISS, RICHARD SAMUEL · 1992 to 2017
$2.7M
Role of BH3-Domain Proteins in the Effector Phase of RAR01AR054796 · NIAMS · SAINT LOUIS UNIVERSITY · PI PERLMAN, HARRIS R · 2008 to 2012
$1.8M
A novel and improved mouse system for studying macrophage specific gene deletionR21AI092490 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PERLMAN, HARRIS R, STEHLIK, CHRISTIAN · 2011 to 2012
$419k
NHLBI NIH HHS HL108795NIAID NIH HHS AI092490NIAMS NIH HHS AR050250NIAMS NIH HHS AR054796NIAMS NIH HHS AR07611NIGMS NIH HHS GM044118NIGMS NIH HHS GM055194
6 · The paper itself

Abstract

backgroundSubstantial advances have been generated in understanding the pathogenesis of rheumatoid arthritis (RA). Current murine models of RA-like disease have provided great insights into the molecular mechanism of inflammatory arthritis due to the use of genetically deficient or transgenic mice. However, these studies are limited by differences that exist between human and murine immune systems. Thus, the development of an animal model that utilizes human immune cells, will afford the opportunity to study their function in the initiation and propagation of inflammatory arthritis.

methodsOne to two-day old irradiated NOD-scid IL2rγ(null) (NSG) mice were reconstituted with human CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and circulating antibodies were determined by ELISA. Arthritis was induced by injecting complete Freund's adjuvant into knee or ankle joints. Mice were also treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed histologically.

resultsHumanized mice were established with high reconstitution rates and were able to spontaneously produce human immunoglobulins as well as specific IgG in response to immunization. Intraperitoneal injection of thioglycolate or injection of complete Freund's adjuvant into joints resulted in migration of human immune cells to the injected sites. Arthritic humanized mice treated with Etanercept had markedly less inflammation, which was associated with decreased total numbers of human CD45+ cells, including human lymphocytes and neutrophils.

conclusionsThe humanized mouse model is a new model to study inflammatory arthritis disease using human leukocytes without rejection of engrafted tissue. Future studies may adapt this system to incorporate RA patient cord blood and develop a chimeric animal model of inflammatory arthritis using genetically predisposed immune cells.

Indexed as

AnimalsAntibodies, Monoclonal, HumanizedArthritis, RheumatoidDisease Models, AnimalFlow CytometryMiceMice, Inbred NODMice, SCIDAntibodies, Monoclonal, Humanized

Identifiers

PMID22974474
PMCPMC3480927

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Registered trials

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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.