Myf-5 m1 /Myf-6 m1 Compound Heterozygous Mouse Mutants Down-regulate Myf-5 Expression and Exert Rib Defects: Evidence for Long-Range cis Effects on Myf-5 Transcription

Myf-5 m1 /Myf-6 m1 Compound Heterozygous Mouse Mutants Down-regulate Myf-5 Expression and Exert... Myf-6 and Myf-5, two members of the family of muscle-specific regulatory genes, are located less than 10 kb apart in the mouse and human genomes. We have shown recently that homozygous mutant mice carrying a pgk-neo-cassette in the first exon of the Myf-6 gene display minor alterations of skeletal musculature but develop a severe rib defect, most likely due to a drastic down-regulation of Myf-5 expression. The mechanism by which the Myf-6 mutation affects the Myf-5 gene is unknown. In order to determine whether Myf-5 transcription is inhibited by the Myf-6 mutation in cis or in trans, we generated compound heterozygous mice carrying inactivated Myf-5 and Myf-6 alleles on different chromosomes. Here, we demonstrate that double-heterozygous mutants exhibit truncated ribs and severe depression of Myf-5 transcription, a phenotype similar to the previously described homozygous Myf-6 mutant mice. These results indicate that the Myf-6 mutation inhibits Myf-5 gene expression by a long-range cis effect. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Developmental Biology Elsevier

Myf-5 m1 /Myf-6 m1 Compound Heterozygous Mouse Mutants Down-regulate Myf-5 Expression and Exert Rib Defects: Evidence for Long-Range cis Effects on Myf-5 Transcription

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Publisher
Elsevier
Copyright
Copyright © 1996 Academic Press
ISSN
0012-1606
eISSN
1095-564X
DOI
10.1006/dbio.1996.0058
pmid
8626014
Publisher site
See Article on Publisher Site

Abstract

Myf-6 and Myf-5, two members of the family of muscle-specific regulatory genes, are located less than 10 kb apart in the mouse and human genomes. We have shown recently that homozygous mutant mice carrying a pgk-neo-cassette in the first exon of the Myf-6 gene display minor alterations of skeletal musculature but develop a severe rib defect, most likely due to a drastic down-regulation of Myf-5 expression. The mechanism by which the Myf-6 mutation affects the Myf-5 gene is unknown. In order to determine whether Myf-5 transcription is inhibited by the Myf-6 mutation in cis or in trans, we generated compound heterozygous mice carrying inactivated Myf-5 and Myf-6 alleles on different chromosomes. Here, we demonstrate that double-heterozygous mutants exhibit truncated ribs and severe depression of Myf-5 transcription, a phenotype similar to the previously described homozygous Myf-6 mutant mice. These results indicate that the Myf-6 mutation inhibits Myf-5 gene expression by a long-range cis effect.

Journal

Developmental BiologyElsevier

Published: Feb 25, 1996

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