C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes.
C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes.
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DOI：
10.1152/physiolgenomics.00106.2009
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发表时间：
2009-12
影响因子：
4.6
通讯作者：
P. Krajacic;J. Hermanowski;O. Lozynska;T. Khurana;Todd Lamitina
中科院分区：
文献类型：
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作者：
P. Krajacic;J. Hermanowski;O. Lozynska;T. Khurana;Todd Lamitina
人类异常蛋白基因突变导致肢体带状肌营养不良2B （LGMD2B）。秀丽隐杆线虫的异铁素同源物fer-1影响精子发育，但目前还不知道在雄性生殖系之外是否表达或有功能作用。通过几种方法，我们发现fe -1 mRNA存在于秀丽隐杆线虫的肌肉细胞中，但不存在于神经元中。在哺乳动物中，肌肉表达异铁蛋白的缺失会导致肌肉表达基因的转录失调。为了确定在秀丽隐杆线虫中是否由于失去肌肉表达的fe -1而引发了类似的基因表达改变，我们对两个功能丧失的fe -1突变体进行了全基因组Affymetrix微阵列分析。两种突变体在基因表达上产生了高度相似的变化，并改变了337个基因的表达。通过多种分析方法，我们发现这个基因集富含已知的调节肌肉结构和功能的基因。然而，这些转录变化似乎并不是对肌肉损伤的反应，因为基因致敏的fer1突变体表现出正常的细丝组织。我们的数据表明，秀丽隐杆线虫肌肉中fer-1的缺失可能会影响肌节稳定性以外的其他过程。因此，秀丽隐杆线虫可能是一个有吸引力的模型系统，可以探索dysferlin蛋白的新的肌肉特异性功能，并深入了解LGMD2B的分子发病机制。
Mutations in the human dysferlin gene cause Limb Girdle Muscular Dystrophy 2B (LGMD2B). The Caenorhabditis elegans dysferlin homolog, fer-1, affects sperms development but is not known to be expressed in or have a functional roles outside of the male germline. Using several approaches, we show that fer-1 mRNA is present in C. elegans muscle cells but is absent from neurons. In mammals, loss of muscle-expressed dysferlin causes transcriptional deregulation of muscle expressed genes. To determine if similar alterations in gene expression are initiated in C. elegans due to loss of muscle-expressed fer-1, we performed whole genome Affymetrix microarray analysis of two loss-of-function fer-1 mutants. Both mutants gave rise to highly similar changes in gene expression and altered the expression of 337 genes. Using multiple analysis methods, we show that this gene set is enriched for genes known to regulate the structure and function of muscle. However, these transcriptional changes do not appear to be in response to gross sarcomeric damage, since genetically sensitized fer-1 mutants exhibit normal thin filament organization. Our data suggest that processes other than sarcomere stability may be affected by loss of fer-1 in C. elegans muscle. Therefore, C. elegans may be an attractive model system in which to explore new muscle-specific functions of the dysferlin protein and gain insights into the molecular pathogenesis of LGMD2B.