Human Molecular Genetics Advance Access published online on March 5, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm022
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Trisomy for the Down syndrome "critical region" is necessary but not sufficient for brain phenotypes of trisomic mice
1 University of Redlands, Redlands, CA 92373 2 Johns Hopkins University School of Medicine, Baltimore, MD 21205 3 Uniformed Services University of the Health Sciences, Bethesda, MD 20814
* Address correspondence to: Roger H. Reeves, Ph.D. Department of Physiology, 725 N. Wolfe St., Johns Hopkins University School of Medicine, Baltimore, MD 21205, TEL 410-955-6621, FAX 443-287-0508, rreeves{at}jhmi.edu
Received January 10, 2007; Revised February 8, 2007; Accepted February 8, 2007
Trisomic Ts65Dn mice show direct parallels with many phenotypes of Down syndrome (DS), including effects on the structure of cerebellum and hippocampus. A small segment of Hsa21 known as the "DS critical region" (DSCR) has been held to contain a gene or genes sufficient to cause impairment in learning and memory tasks involving the hippocampus. To test this hypothesis, we developed Ts1Rhr and Ms1Rhr mouse models that are respectively trisomic and monosomic for this region. Here we show that trisomy for the DSCR alone is not sufficient to produce the structural and functional features of hippocampal impairment that are seen in the Ts65Dn mouse and in DS. However, when the critical region is returned to normal dosage in trisomic Ms1Rhr/Ts65Dn mice, performance in the Morris water maze is identical to euploid, demonstrating that this region is necessary for the phenotype. Thus, while the prediction of the critical region hypothesis was disproved, novel gene dosage effects were identified which help to define how trisomy for this segment of the chromosome contributes to phenotypes of DS.
4 Current address: Dept. of Biology, Indiana University-Purdue University at Indianapolis, Indianapolis, IN
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|