Skip Navigation


Human Molecular Genetics Advance Access originally published online on June 25, 2007
Human Molecular Genetics 2007 16(17):2040-2052; doi:10.1093/hmg/ddm152
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
16/17/2040    most recent
ddm152v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Google Scholar
Right arrow Articles by Besson, V.
Right arrow Articles by Hérault, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Besson, V.
Right arrow Articles by Hérault, Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

©2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses

Vanessa Besson1, Véronique Brault1, Arnaud Duchon1, Dieudonné Togbe1, Jean-Charles Bizot2, Valérie F.J. Quesniaux1, Bernard Ryffel1 and Yann Hérault1,*

1 Institut de Transgenose, Molecular Immunology and Embryology, UMR6218, CNRS, Université Orléans, 3B rue de la Férollerie, Orléans, Cedex 2 45071, France and 2 Key-Obs SA, 45150 Orléans, France

* To whom correspondence should be addressed. Tel/Fax: +33 238257930; Email: herault{at}cnrs-orleans.fr

Received May 11, 2007; Accepted June 14, 2007

Monosomy 21 is a rare human disease due to gene dosage errors disturbing a variety of physiological and morphological systems including brain, skeletal, immune and respiratory functions. Most of the human condition corresponds to partial or mosaic monosomy suggesting that Monosomy 21 may be lethal. In order to search for dosage-sensitive genes involved in the human pathology, we generated by chromosomal engineering a monosomic mouse for the Prmt2–Col6a1 interval corresponding to the most telomeric part of human chromosome 21. Haploinsufficiency of the 13 genes, located in the 0.5 Mb genetic interval and conserved in man and mouse, caused apparently no morphological defect as observed in patients. However, monosomic mice displayed an enhanced inflammatory response after local intranasal lipopolysaccharide administration with enhanced recruitment of neutrophils and secretion of cytokines such as tumor necrosis factor-{alpha} (TNF-{alpha}), IL-1ß, IL-12p70 and IFN-{gamma} in the lung as well increased TNF-{alpha} production after systemic administration. Further analysis demonstrates that monosomic macrophages were involved and that a few genes, Prmt2, Pcnt2, Mcm3ap and Lss located in the region were candidate for the inflammatory response. Altogether, these results demonstrate the existence of dosage-sensitive genes in the Prmt2–Col6a1 region that control the inflammation and the lung function. Furthermore, they point out that similar partial Monosomies 21 in human might have eluded the diagnosis due to the very specific defects observed in this murine model.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.