Narushima Y, Unno M, Nakagawara K, Mori M, Miyashita H, Suzuki Y, Noguchi N, Takasawa S, Kumagai T, Yonekura H, Okamoto H
Department of Biochemistry, Tohoku University School of Medicine, Miyagi, Japan.
Gene. 1997 Feb 7;185(2):159-68. doi: 10.1016/s0378-1119(96)00589-6.
Reg (regenerating gene), first isolated from a rat regenerating islet cDNA library, is expressed in regenerating islet beta-cells. Recently, it has been revealed that Reg and Reg-related genes constitute a multigene family, Reg family, which consists of three subtypes (type I, II, III) based on the primary structures of the encoded proteins of the genes. In mouse, type I and type II Reg genes (i.e. RegI and RegII gene) have so far been isolated. In the present study, the complete nucleotide (nt) sequences of the cDNAs and genes encoding murine type III Reg (regenerating gene product), RegIII alpha, RegIII beta and RegIII gamma were determined. RegIII alpha, RegIII beta and RegIII gamma encode 175-, 175- and 174-amino acid (aa) proteins, respectively, with 60-70% homology. All three genes are composed of six exons and five introns spanning approx. 3 kb, and exhibit distinctive structural features unique for members of the Reg gene family. All the mouse Reg genes, RegIII alpha, RegIII beta, RegIII gamma, RegI and RegII, are assigned to the adjacent site of chromosome 6C by fluorescence in situ hybridization (FISH). RegIII alpha, RegIII beta and RegIII gamma were expressed weakly in pancreas, strongly in intestinal tract, but not in hyperplastic islets, whereas both RegI and RegII were expressed in hyperplastic islets. These results suggest that genes of the mouse Reg family are derived from a common ancestor gene by several gene duplications, and have obtained divergency in expression and function in the process of genetic evolution.
Reg（再生基因）最初是从大鼠再生胰岛cDNA文库中分离出来的，在再生胰岛β细胞中表达。最近发现，Reg及与Reg相关的基因构成了一个多基因家族，即Reg家族，该家族根据基因编码蛋白的一级结构分为三个亚型（I型、II型、III型）。在小鼠中，目前已分离出I型和II型Reg基因（即RegI和RegII基因）。在本研究中，测定了编码小鼠III型Reg（再生基因产物）、RegIIIα、RegIIIβ和RegIIIγ的cDNA和基因的完整核苷酸（nt）序列。RegIIIα、RegIIIβ和RegIIIγ分别编码175、175和174个氨基酸（aa）的蛋白质，同源性为60%-70%。这三个基因均由六个外显子和五个内含子组成，跨度约为3kb，并表现出Reg基因家族成员独特的结构特征。通过荧光原位杂交（FISH），所有小鼠Reg基因，即RegIIIα、RegIIIβ、RegIIIγ、RegI和RegII，都被定位到6C染色体的相邻位点。RegIIIα、RegIIIβ和RegIIIγ在胰腺中弱表达，在肠道中强表达，但在增生性胰岛中不表达，而RegI和RegII在增生性胰岛中均有表达。这些结果表明，小鼠Reg家族的基因是通过多次基因复制从一个共同的祖先基因衍生而来的，并且在基因进化过程中在表达和功能上出现了分歧。
