| Autor: |
Walz, Katherina, Caratini-Rivera, Sandra, Weimin Bi, Fonseca, Patricia, Mansouri, Dena L., Lynch, Jennifer, Vogel, Hannes, Noebels, Jeffrey L., Bradley, Allan, Lupski, James R. |
| Předmět: |
|
| Zdroj: |
Molecular & Cellular Biology; May2003, Vol. 23 Issue 10, p3646, 10p, 15 Color Photographs, 5 Black and White Photographs, 12 Diagrams, 2 Charts, 2 Graphs |
| Abstrakt: |
Contiguous gene syndromes (CGS) are a group of disorders associated with chromosomal rearrangements of which the phenotype is thought to result from altered copy numbers of physically linked dosage-sensitive genes. Smith-Magenis syndrome (SMS) is a CGS associated with a deletion within band p11.2 of chromosome 17. Recently, patients harboring the predicted reciprocal duplication product [dup(17)(p11.2p11.2)] have been described as having a relatively mild phenotype. By chromosomal engineering, we created rearranged chromosomes carrying the deletion [Df(11)17] or duplication [Dp(11)17] of the syntenic region on mouse chromosome 11 that spans the genomic interval commonly deleted in SMS patients. Df(11)17/+ mice exhibit craniofacial abnormalities, seizures, marked obesity, and male-specific reduced fertility. Dp(11)17/+ animals are underweight and do not have seizures, craniofacial abnormalities, or reduced fertility. Examination of Df(11)17/Dp(11)17 animals suggests that most of the observed phenotypes result from gene dosage effects. Our murine models represent a powerful tool to analyze the consequences of gene dosage imbalance in this genomic interval and to investigate the molecular genetic bases of both SMS and dup(17)(p11.2p11.2). [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
