Skip Navigation



Human Molecular Genetics Advance Access published online on September 30, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh288
© 2004 by Oxford University Press
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
13/21/2613    most recent
ddh288v1
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 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 arrowRequest Permissions
Google Scholar
Right arrow Articles by Yan, J.
Right arrow Articles by Lupski, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yan, J.
Right arrow Articles by Lupski, J. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Article

Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome

Jiong Yan 1, Victoria W. Keener 1, Weimin Bi 1, Katherina Walz 1, Allan Bradley 2, Monica J. Justice 1, and James R. Lupski 3*

1 Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030 USA
2 The Wellcome Trust Sanger Institute, Hinxton, UK
3 Department of Molecular and Human Genetics, Baylor College of Medicine, Room 604B, One Baylor Plaza, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA; Texas Children's hospital, Houston, Texas, USA

* To whom correspondence should be addressed. E-mail: jlupski{at}bcm.tmc.edu.


  Abstract

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with del(17)(p11.2p11.2). The phenotype is variable even in patients with deletion of the same size. RAI1 has been recently suggested as a major gene for the majority of the SMS phenotype, but its role in the full spectrum of the phenotype remains unclear. Df(11)17/+ mice contain a heterozygous deletion in the mouse region syntenic to the SMS common deletion, and exhibit craniofacial abnormalities, seizures, and marked obesity, partially reproducing the SMS phenotype. To further study the genetic basis for the phenotype, we constructed three lines of mice with smaller deletions (Df(11)17-1, Df(11)17-2, and Df(11)17-3) using retrovirus mediated chromosome engineering to create nested deletion. Both craniofacial abnormalities and obesity have been observed, but the penetrance of the craniofacial phenotype was markedly reduced in comparison to Df(11)17/+ mice. Overt seizures were not observed. Phenotypic variation has been observed in mice with the same deletion size in both the same and different genetic backgrounds, which may reflect the variation documented in the patients. These results indicate that the smaller deletions contain the gene(s), most likely Rai1, for the craniofacial abnormalities and obesity. However, genes or regulatory elements in the larger deletion that are not located in the smaller deletions, as well as genes located elsewhere, also influence both the penetrance and expressivity of the phenotype. Our mouse models refined the genomic region important for a portion of the SMS phenotype and provided a basis for further molecular analysis of genes associated with SMS.


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


This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
M. Dierssen, Y. Herault, and X. Estivill
Aneuploidy: From a Physiological Mechanism of Variance to Down Syndrome
Physiol Rev, July 1, 2009; 89(3): 887 - 920.
[Abstract] [Full Text] [PDF]

Home page
 DMMHome page
D. Nguyen and T. Xu
The expanding role of mouse genetics for understanding human biology and disease
Dis. Model. Mech., July 1, 2008; 1(1): 56 - 66.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
W. Bi, J. Yan, X. Shi, L. A. Yuva-Paylor, B. A. Antalffy, A. Goldman, J. W. Yoo, J. L. Noebels, D. L. Armstrong, R. Paylor, et al.
Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas Rai1 heterozygous mice display minimal behavioral phenotypes
Hum. Mol. Genet., August 1, 2007; 16(15): 1802 - 1813.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
A. M. Goldman, L. Potocki, K. Walz, J. K. Lynch, D. G. Glaze, J. R. Lupski, and J. L. Noebels
Topical Review: Epilepsy and Chromosomal Rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)]
J Child Neurol, February 1, 2006; 21(2): 93 - 98.
[Abstract] [PDF]

Home page
 Genome ResHome page
J. L. Guenet
The mouse genome
Genome Res., December 1, 2005; 15(12): 1729 - 1740.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
W. Bi, T. Ohyama, H. Nakamura, J. Yan, J. Visvanathan, M. J. Justice, and J. R. Lupski
Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome
Hum. Mol. Genet., April 15, 2005; 14(8): 983 - 995.
[Abstract] [Full Text] [PDF]


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.