Linkage, evolution, and expression of the rat apolipoprotein A-I, C-III, and A-IV genes.
Linkage, evolution, and expression of the rat apolipoprotein A-I, C-III, and A-IV genes.
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DOI：
10.1016/s0021-9258(18)69300-7
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发表时间：
1986-10
期刊：
影响因子：
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通讯作者：
I. Haddad;J. Ordovás;T. Fitzpatrick;S. Karathanasis
中科院分区：
文献类型：
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作者：
I. Haddad;J. Ordovás;T. Fitzpatrick;S. Karathanasis
编码脂质转运系统的三种蛋白质的基因，载脂蛋白A-I（apoA-I）、C-III（apoC-III）和A-IV（apoA-IV），在人类基因组中紧密相连并串联组织为多基因家族。这个多基因家族的进化进行了研究，通过克隆和广泛的限制性酶切图谱分析约20-脱氢酶基因组DNA片段含有大鼠apoA-I基因。使用人apoC-III和apoA-IV cDNA探针对该DNA片段进行低严格性杂交印迹分析，结果显示apoA-I、apoC-III和apoA-IV基因在大鼠基因组中也是紧密连锁和串联组织的。大鼠apoA-I，apoC-III和apoA-IV基因的完整表征表明，它们的相对位置，大小，转录方向和内含子-外显子组织与相应的人类基因非常相似。使用相应的基因探针，通过组织总RNA的定量斑点杂交，测定大鼠各种组织中apoA-I、apoC-III和apoA-IV mRNA的相对稳态水平。成人肝脏和肠，但不包括结肠、脑、脾、肌肉、心脏、肺和肾脏，含有apoA-I、apoC-III和apoA-IV mRNA。胎儿肝脏和小肠含有apoA-I，但不含apoC-III或apoA-IV mRNA。在新生儿发育过程中，肝脏含有apoA-I和apoC-III，但不含apoA-IV，而肠道含有apoA-I、apoC-III和大量的apoA-IV mRNA。在成年期和衰老期间，肝脏和肠道都含有所有三种apoA-I，apoC-III和apoA-IV mRNA。这些结果表明载脂蛋白A-I/C-III/A-IV多基因家族在哺乳动物辐射之前就已建立，并表明这些基因在所有哺乳动物的基因组中具有相似的组织结构。此外，这些结果表明，大鼠apoA-I，apoC-III和apoA-IV基因的表达是肝脏和肾脏特异性的，并受胎儿，新生儿和衰老相关因素的调节。
The genes coding for three of the proteins of the lipid transport system, apolipoproteins A-I (apoA-I), C-III (apoC-III), and A-IV (apoA-IV), are closely linked and tandemly organized as a multigene family in the human genome. The evolution of this multigene family was studied by cloning and extensive restriction mapping analysis of an approximately 20-kilobase genomic DNA fragment containing the rat apoA-I gene. Low stringency hybridization blotting analysis of this DNA fragment using human apoC-III and apoA-IV cDNA probes revealed that the apoA-I, apoC-III, and apoA-IV genes are also closely linked and tandemly organized in the rat genome. Complete characterization of the rat apoA-I, apoC-III, and apoA-IV genes showed that their relative location, size, direction of transcription, and intron-exon organization are remarkably similar to those of the corresponding human genes. The relative steady state apoA-I, apoC-III, and apoA-IV mRNA levels in various rat tissues were determined by quantitative dot blot hybridization of tissue total RNA using the corresponding gene probes. Adult liver and intestine, but not colon, brain, spleen, muscle, heart, lung, and kidney, contain apoA-I, apoC-III, and apoA-IV mRNAs. Fetal liver and intestine contain apoA-I but not apoC-III or apoA-IV mRNAs. During neonatal development the liver contains apoA-I and apoC-III but not apoA-IV while the intestine contains apoA-I, apoC-III, and substantial amounts of apoA-IV mRNAs. In adulthood and during aging both liver and intestine contain all three apoA-I, apoC-III, and apoA-IV mRNAs. These results indicate that the apolipoprotein A-I/C-III/A-IV multigene family was established before mammalian radiation and suggest that these genes are similarly organized in the genomes of all mammals. In addition, these results indicate that expression of the rat apoA-I, apoC-III, and apoA-IV genes is liver- and intestine-specific and regulated by fetal-, neonatal-, and aging-related factors.