STRUCTURE, CHROMOSOMAL LOCALIZATION AND EXPRESSION OF MOUSE GENES ENCODING TYPE-III REG, REGIII-ALPHA, REGIII-BETA, REGIII-GAMMA

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 mult igene 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 gen e) have so far been isolated. In the present study, the complete nucle otide (nt) sequences of the cDNAs and genes encoding murine type III R eg (regenerating gene product), RegIII alpha, RegIII beta and RegIII g amma were determined. RegIII alpha, RegIII beta and RegIII gamma encod e 175-, 175- and 174-amino acid (aa) proteins, respectively, with 60-7 0% homology. All three genes are composed of six exons and five intron s spanning approx. 3 kb, and exhibit distinctive structural features u nique for members of the Reg gene family. All the mouse Reg genes, Reg III alpha, RegIII beta, RegIII gamma, RegI and RegII, are assigned to the adjacent site of chromosome 6C by fluorescence in situ hybridizati on (FISH). RegIII alpha, RegIII beta and RegIII gamma were expressed w eakly in pancreas, strongly in intestinal tract, but not in hyperplast ic islets, whereas both RegI and RegII were expressed in hyperplastic islets. These results suggest that genes of the mouse Reg family are d erived from a common ancestor gene by several gene duplications, and h ave obtained divergency in expression and function in the process of g enetic evolution.