Duplication of the Hoxd11 gene causes alterations in the axial and appendicular skeleton of the mouse.

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Oncological Sciences; Biology; Human Genetics
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Capecchi, Mario R.
Other Author Boulet, Anne M.
Title Duplication of the Hoxd11 gene causes alterations in the axial and appendicular skeleton of the mouse.
Date 2002-09-01
Description The Hox genes encode a group of transcription factors essential for proper development of the mouse. Targeted mutation of the Hoxd11 gene causes reduced male fertility, vertebral transformation, carpal bone fusions, and reductions in digit length. A duplication of the Hoxd11 gene was created with the expectation that the consequences of restricted overexpression in the appropriate cells would provide further insight into the function of the Hoxd11 gene product. Genetic assays demonstrated that two tandem copies of Hoxd11 were functionally indistinguishable from the normal two copies of the gene on separate chromosomes with respect to formation of the axial and appendicular skeleton. Extra copies of Hoxd11 caused an increase in the lengths of some bones of the forelimb autopod and a decrease in the number of lumbar vertebrae. Further, analysis of the Hoxd11 duplication demonstrated that the Hoxd11 protein can perform some functions supplied by its paralogue Hoxa11. For example, the defects in forelimb bones are corrected when extra copies of Hoxd11 are present in the Hoxa11 homozygous mutant background. Thus, it appears that Hoxd11 can quantitatively compensate for the absence of Hoxa11 protein, and therefore Hoxa11 and Hoxd11 are functionally equivalent in the zeugopod. However, extra copies of Hoxd11 did not improve male or female fertility in Hoxa11 mutants. Interestingly, the insertion of an additional Hoxd11 locus into the HoxD complex does not appear to affect the expression patterns of the neighboring Hoxd10, -d12, or -d13 genes.
Type Text
Publisher Academic Press Ltd.
Volume 249
Issue 1
First Page 96
Last Page 107
Subject Animals; Bone Development; Forelimb; Gene Expression Regulation, Developmental
Subject MESH Gene Duplication; Homeodomain Proteins; Oncogene Proteins; Zebrafish Proteins
Language eng
Bibliographic Citation Dev Biol. 2002 Sep 1;249(1):96-107. Boulet AM, Capecchi MR. Duplication of the Hoxd11 gene causes alterations in the axial and appendicular skeleton of the mouse. Retrieved on November 1 2006 from http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WDG-46P41WJ-8&_coverDate=09%2F01%2F2002&_alid=479336567&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6766&_sort=d&view=c&_acct=C000049956&_version=1&_urlVersion=0&_userid=990933&md5=4dbf1c9c3337580f1d7337594213fc46.
Rights Management copyright © 2002 Academic Press Ltd. All Rights Reserved.
Format Medium application/pdf
Identifier ir-main,523
ARK ark:/87278/s6fb5mh2
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 706234
Reference URL https://collections.lib.utah.edu/ark:/87278/s6fb5mh2
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