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-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.
Floss
T
T
Department of Cell and Molecular Biology, University of Braunschweig, Federal Republic of Germany.
Arnold
H H
HH
Braun
T
T
D000818:Animals; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000502:physiology*; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012272:Ribs / Q000196:embryology*; D015534:Trans-Activators; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D015534:Trans-Activators; C063403:myogenic factor 6