Home LiteratureArticle Details

PMID: 15499018 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A chromosome 21 critical region does not cause specific Down syndrome phenotypes.

Science (New York, N.Y.) ·Vol. 306 ·No. 5696 ·2004-10-22 ·Pages 687-90

Olson LE, Richtsmeier JT, Leszl J, Reeves RH

Abstract

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.

MeSH Terms

Animals Chromosome Deletion Chromosomes, Human, Pair 21/genetics Chromosomes, Mammalian/genetics Craniofacial Abnormalities/genetics Crosses, Genetic Disease Models, Animal Down Syndrome/genetics,pathology Female Gene Dosage Gene Duplication Gene Targeting Genetic Vectors Humans Karyotyping Male Mandible/abnormalities Mice Mice, Inbred C57BL Monosomy Phenotype Recombination, Genetic Skull/abnormalities Trisomy

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Olson L E

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Richtsmeier J T

Leszl J

Reeves R H

References (13)

13 references, click to expand

Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities.
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6256-61 PMID: 9600952
Down syndrome phenotypes: the consequences of chromosomal imbalance.
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4997-5001 PMID: 8197171
Molecular genetic approach to the characterization of the "Down syndrome region" of chromosome 21.
Genomics. 1989 Aug;5(2):325-31 PMID: 2529205
Down syndrome--a disruption of homeostasis.
Am J Med Genet. 1983 Feb;14(2):241-69 PMID: 6220605
Molecular mapping of twenty-four features of Down syndrome on chromosome 21.
Eur J Hum Genet. 1993;1(2):114-24 PMID: 8055322
Chromosome engineering in mice.
Nature. 1995 Dec 14;378(6558):720-4 PMID: 7501018
Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice.
Dev Dyn. 2000 Feb;217(2):137-45 PMID: 10706138
The DNA sequence of human chromosome 21.
Nature. 2000 May 18;405(6784):311-9 PMID: 10830953
Too much of a good thing: mechanisms of gene action in Down syndrome.
Trends Genet. 2001 Feb;17(2):83-8 PMID: 11173117
A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome.
Science. 2002 May 31;296(5573):1661-71 PMID: 12040188
Down's syndrome. The possibility of a pathogenetic segment on chromosome no. 21.
Humangenetik. 1974 Jan 22;21(1):99-101 PMID: 4276065
Mouse models of Down syndrome: how useful can they be? Comparison of the gene content of human chromosome 21 with orthologous mouse genomic regions.
Gene. 2003 Oct 30;318:137-47 PMID: 14585506
Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase 1.
Cancer Res. 2003 Oct 15;63(20):6602-6 PMID: 14583452

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1098992

Published

2004-10-22

Pages

687-90

Language

English

Region

United States

NLM ID

0404511

PMCID

PMC4019810

Subset

Grants

NICHD NIH HHS · HD38384 · United States

NICHD NIH HHS · R01 HD038384 · United States

NICHD NIH HHS · P01 HD024605 · United States

NIDCR NIH HHS · F33 DE005706 · United States

NICHD NIH HHS · HD24605 · United States

Corrections

CommentIn

PMID: 15499000

External Links

PubMed source DOI: 10.1126/science.1098992 PMC Full Text View journal details

Analysis Services

A chromosome 21 critical region does not cause specific Down syndrome phenotypes.

Contact

WeChat Official Account