Bio Forum & Bio Expo Japan Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on March 8, 2005, 10.1073/pnas.0500802102
PNAS | March 22, 2005 | vol. 102 | no. 12 | 4500-4505
OPEN ACCESS ARTICLE


This Article
Free via Open Access: OA
Right arrow Figures Only
Right arrow OA Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
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 File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vacík, T.
Right arrow Articles by Forejt, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vacík, T.
Right arrow Articles by Forejt, J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

GENETICS
Segmental trisomy of chromosome 17: A mouse model of human aneuploidy syndromes

Tomás Vacík *, Michael Ort {dagger}, {ddagger}, Sona Gregorová *, Petr Strnad *, Radek Blatny *, Nathalie Conte §, Allan Bradley §, Jan Bures {dagger}, and Jirí Forejt *, ¶

Institutes of *Molecular Genetics and {dagger}Physiology, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic; {ddagger}Department of Psychiatry, First School of Medicine, Charles University, 11636 Prague, Czech Republic; and §The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom

Contributed by Jan Bures, January 31, 2005

Triplication of whole autosomes or large autosomal segments is detrimental to the development of a mammalian embryo. The trisomy of human chromosome (Chr) 21, known as Down's syndrome, is regularly associated with mental retardation and a variable set of other developmental anomalies. Several mouse models of Down's syndrome, triplicating 33–104 genes of Chr16, were designed in an attempt to analyze the contribution of specific orthologous genes to particular developmental features. However, a recent study challenged the concept of dosage-sensitive genes as a primary cause of an abnormal phenotype. To distinguish between the specific effects of dosage-sensitive genes and nonspecific effects of a large number of arbitrary genes, we revisited the mouse Ts43H/Ph segmental trisomy. It encompasses >310 known genes triplicated within the proximal 30 megabases (Mb) of Chr17. We refined the distal border of the trisomic segment to the interval bounded by bacterial artificial chromosomes RP23-277B13 (location 29.0 Mb) and Cbs gene (location 30.2 Mb). The Ts43H mice, viable on a mixed genetic background, exhibited spatial learning deficits analogous to those observed in Ts65Dn mice with unrelated trisomy. Quantitative analysis of the brain expression of 20 genes inside the trisomic interval and 12 genes lying outside on Chr17 revealed 1.2-fold average increase of mRNA steady-state levels of triplicated genes and 0.9-fold average down-regulation of genes beyond the border of trisomy. We propose that systemic comparisons of unrelated segmental trisomies, such as Ts65Dn and Ts43H, will elucidate the pathways leading from the triplicated sequences to the complex developmental traits.

dosage-sensitive genes | Down's syndrome | Morris water maze | mouse segmental trisomy | quantitative RT-PCR

Author contributions: J.B. and J.F. designed research; T.V., M.O., S.G., R.B., N.C., and J.F. performed research; T.V., M.O., S.G., P.S., R.B., N.C., A.B., J.B., and J.F. analyzed data; N.C. and A.B. contributed new reagents/analytic tools; and J.B. and J.F. wrote the paper.

Freely available online through the PNAS open access option.

Abbreviations: BAC, bacterial artificial chromosome; CGH, comparative genome hybridization; Chr, chromosome; DS, Down's syndrome; Mb, megabases; SNuPE, single nucleotide primer extension assay.

To whom correspondence should be addressed. E-mail: jforejt{at}biomed.cas.cz.

© 2005 by The National Academy of Sciences of the USA


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


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 Genome Res.Home page
D. Homolka, R. Ivanek, J. Capkova, P. Jansa, and J. Forejt
Chromosomal rearrangement interferes with meiotic X chromosome inactivation
Genome Res., October 1, 2007; 17(10): 1431 - 1437.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
V. Besson, V. Brault, A. Duchon, D. Togbe, J.-C. Bizot, V. F.J. Quesniaux, B. Ryffel, and Y. Herault
Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses
Hum. Mol. Genet., September 1, 2007; 16(17): 2040 - 2052.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
V. L.J. Tybulewicz and E. M.C. Fisher
New techniques to understand chromosome dosage: mouse models of aneuploidy
Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R103 - R109.
[Abstract] [Full Text] [PDF]