Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 22 October 2004:
Vol. 306. no. 5696, pp. 687 - 690
DOI: 10.1126/science.1098992
Prev | Table of Contents | Next

Reports

A Chromosome 21 Critical Region Does Not Cause Specific Down Syndrome Phenotypes

L. E. Olson,1* J. T. Richtsmeier,2 J. Leszl,2 R. H. Reeves1{dagger}

The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported to contain genes responsible for many features of Down syndrome (DS), including craniofacial dysmorphology. We used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR and assessed dysmorphologies of the craniofacial skeleton that show direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes were not sufficient and were largely not necessary to produce the facial phenotype. These results refute specific predictions of the prevailing hypothesis of gene action in DS.

1 Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Department of Anthropology and Program in Genetics, Pennsylvania State University, University Park, PA 16802, USA.



* Present address: Department of Biology, University of Redlands, Redlands, CA 92373, USA.

{dagger} To whom correspondence should be addressed. E-mail: rreeves{at}jhmi.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Upregulation of three Drosophila homologs of human chromosome 21 genes alters synaptic function: Implications for Down syndrome.
K. T. Chang and K.-T. Min (2009)
PNAS 106, 17117-17122
   Abstract »    Full Text »    PDF »
The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies.
J. O. Korbel, T. Tirosh-Wagner, A. E. Urban, X.-N. Chen, M. Kasowski, L. Dai, F. Grubert, C. Erdman, M. C. Gao, K. Lange, et al. (2009)
PNAS 106, 12031-12036
   Abstract »    Full Text »    PDF »
Aneuploidy: From a Physiological Mechanism of Variance to Down Syndrome.
M. Dierssen, Y. Herault, and X. Estivill (2009)
Physiol Rev 89, 887-920
   Abstract »    Full Text »    PDF »
The "Down Syndrome Critical Region" Is Sufficient in the Mouse Model to Confer Behavioral, Neurophysiological, and Synaptic Phenotypes Characteristic of Down Syndrome.
N. P. Belichenko, P. V. Belichenko, A. M. Kleschevnikov, A. Salehi, R. H. Reeves, and W. C. Mobley (2009)
J. Neurosci. 29, 5938-5948
   Abstract »    Full Text »    PDF »
Down syndrome--recent progress and future prospects.
F. K. Wiseman, K. A. Alford, V. L.J. Tybulewicz, and E. M.C. Fisher (2009)
Hum. Mol. Genet. 18, R75-R83
   Abstract »    Full Text »    PDF »
Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome.
S. Malinge, S. Izraeli, and J. D. Crispino (2009)
Blood 113, 2619-2628
   Abstract »    Full Text »    PDF »
Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome.
F. Liu, Z. Liang, J. Wegiel, Y.-W. Hwang, K. Iqbal, I. Grundke-Iqbal, N. Ramakrishna, and C.-X. Gong (2008)
FASEB J 22, 3224-3233
   Abstract »    Full Text »    PDF »
Highly penetrant myeloproliferative disease in the Ts65Dn mouse model of Down syndrome.
G. Kirsammer, S. Jilani, H. Liu, E. Davis, S. Gurbuxani, M. M. Le Beau, and J. D. Crispino (2008)
Blood 111, 767-775
   Abstract »    Full Text »    PDF »
Modeling the monosomy for the telomeric part of human chromosome 21 reveals haploinsufficient genes modulating the inflammatory and airway responses.
V. Besson, V. Brault, A. Duchon, D. Togbe, J.-C. Bizot, V. F.J. Quesniaux, B. Ryffel, and Y. Herault (2007)
Hum. Mol. Genet. 16, 2040-2052
   Abstract »    Full Text »    PDF »
Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities.
Z. Li, T. Yu, M. Morishima, A. Pao, J. LaDuca, J. Conroy, N. Nowak, S.-I. Matsui, I. Shiraishi, and Y. E. Yu (2007)
Hum. Mol. Genet. 16, 1359-1366
   Abstract »    Full Text »    PDF »
Trisomy for the Down syndrome 'critical region' is necessary but not sufficient for brain phenotypes of trisomic mice.
L. E. Olson, R. J. Roper, C. L. Sengstaken, E. A. Peterson, V. Aquino, Z. Galdzicki, R. Siarey, M. Pletnikov, T. H. Moran, and R. H. Reeves (2007)
Hum. Mol. Genet. 16, 774-782
   Abstract »    Full Text »    PDF »
Ts65Dn, a Mouse Model of Down Syndrome, Exhibits Increased GABAB-Induced Potassium Current.
T. K. Best, R. J. Siarey, and Z. Galdzicki (2007)
J Neurophysiol 97, 892-900
   Abstract »    Full Text »    PDF »
New techniques to understand chromosome dosage: mouse models of aneuploidy.
V. L.J. Tybulewicz and E. M.C. Fisher (2006)
Hum. Mol. Genet. 15, R103-R109
   Abstract »    Full Text »    PDF »
Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells.
M. W. Lensch and G. Q. Daley (2006)
Blood 107, 2605-2612
   Abstract »    Full Text »    PDF »
An Aneuploid Mouse Strain Carrying Human Chromosome 21 with Down Syndrome Phenotypes.
A. O'Doherty, S. Ruf, C. Mulligan, V. Hildreth, M. L. Errington, S. Cooke, A. Sesay, S. Modino, L. Vanes, D. Hernandez, et al. (2005)
Science 309, 2033-2037
   Abstract »    Full Text »    PDF »
Dissecting the genetic complexity of human 6p deletion syndromes by using a region-specific, phenotype-driven mouse screen.
D. Bogani, C. Willoughby, J. Davies, K. Kaur, G. Mirza, A. Paudyal, H. Haines, R. McKeone, M. Cadman, G. Pieles, et al. (2005)
PNAS 102, 12477-12482
   Abstract »    Full Text »    PDF »
Segmental trisomy of chromosome 17: A mouse model of human aneuploidy syndromes.
T. Vacik, M. Ort, S. Gregorova, P. Strnad, R. Blatny, N. Conte, A. Bradley, J. Bures, and J. Forejt (2005)
PNAS 102, 4500-4505
   Abstract »    Full Text »    PDF »
The Goldilocks Genes.
M. Leslie (2004)
Sci. Aging Knowl. Environ. 2004, ns8
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)