Floss T, Arnold H H, Braun T
Department of Cell and Molecular Biology, University of Braunschweig, Federal Republic of Germany.
Dev Biol. 1996 Feb 25;174(1):140-7. doi: 10.1006/dbio.1996.0058.
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.
Myf-6和Myf-5是肌肉特异性调节基因家族的两个成员，在小鼠和人类基因组中，它们的位置相隔不到10千碱基对。我们最近发现，在Myf-6基因的第一个外显子中携带pgk-neo盒的纯合突变小鼠，其骨骼肌组织仅有轻微改变，但会出现严重的肋骨缺陷，这很可能是由于Myf-5表达的急剧下调所致。Myf-6突变影响Myf-5基因的机制尚不清楚。为了确定Myf-5转录是在顺式还是反式中被Myf-6突变抑制，我们培育了在不同染色体上携带失活的Myf-5和Myf-6等位基因的复合杂合小鼠。在此，我们证明双杂合突变体表现出肋骨截断和Myf-5转录的严重抑制，这一表型与先前描述的纯合Myf-6突变小鼠相似。这些结果表明，Myf-6突变通过长距离顺式效应抑制Myf-5基因表达。
