Genomic organization and expression analysis of the murine Fam3c gene
Genomic organization and expression analysis of the murine Fam3c gene
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DOI：
10.1016/j.gene.2004.03.026
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发表时间：
2004-06-23
期刊：
影响因子：
3.5
通讯作者：
Greinwald, JH
中科院分区：
文献类型：
--
作者：
Pilipenko, VV;Reece, A;Greinwald, JH
此前，我们将 FAM3C 鉴定为常染色体隐性遗传非综合征性听力损失基因座 17 (DFNB17) 的候选基因。此后该基因被发现是细胞因子样基因家族的成员，但其功能尚未确定。因此，本研究的目的是阐明基因结构和表达模式，提供可能允许建立有关内耳 FAM3C 功能的假设的信息。为此，我们分析了其小鼠直系同源物 Fam3c。发现 Fam3c 在所有分析的组织中普遍表达，并且具有两种主要的转录物变体，推测是由两种不同的聚腺苷酸化信号的替代使用引起的。原位杂交实验揭示了胚胎第 (E) 15.5 天生长的半规管非感觉上皮中 Fam3c 的主要表达模式。这种表达模式类似于 Nkx5 同源盒基因的已知模式。对 Fam3c 启动子区域的分析证明了推定的 Nkx5.1 结合位点。根据我们的发现，我们假设 Fam3c 可能是 Nkx5.1 转录因子的下游靶基因，因此可能参与内耳胚胎发生过程中的细胞分化和增殖。此外，对FAM3C直系同源蛋白的推定氨基酸序列的分析表明，它们的一级和二级结构以及整体拓扑结构是高度保守的。进一步的研究正在进行中，以确定 FAM3C 在内耳发育中的作用。
Previously, we identified FAM3C as a candidate gene for autosomal recessive nonsyndromic hearing loss locus 17 (DFNB17). This gene has since been found to be a member of a cytokine-like gene family, but its function has not been determined. The purpose of this study was thus to elucidate the gene structure and pattern of expression, providing information that might allow a hypothesis to be developed about FAM3C function of in the inner ear. To do this we analyzed its mouse ortholog, Fam3c. Fam3c was found to be ubiquitously expressed in all analyzed tissues, and had two major transcript variants presumed to result from an alternative use of two distinct polyadenylation signals. In situ hybridization experiments revealed a predominant Fam3c pattern of expression in the nonsensory epithelium of the growing semicircular canals at embryonic day (E) 15.5. This expression pattern resembles the known pattern of the Nkx5 homeobox genes. Analysis of the Fam3c promoter region demonstrated a putative Nkx5.1 binding site. Based on our findings, we hypothesize that Fam3c may be a downstream target gene for the Nkx5.1 transcription factor, and may thus be involved in cell differentiation and proliferation during inner ear embryogenesis. Additionally, analyses of putative amino acid sequences of FAM3C orthologous proteins showed that their primary and secondary structures and overall topology were highly conserved. Further study is underway to determine the role of FAM3C in inner ear development.