Identification of a novel Reg family gene, Reg IIIδ, and mapping of all three types of Reg family gene in a 75 kilobase mouse genomic region

Regenerating gene (Reg), first isolated from a regenerating islet cDNA library, encodes a secretory protein with a growth stimulating effect on pancreatic beta cells that ameliorates the diabetes of 90% depancreatized rats and non-obese diabetic mice. Rrg and Reg-related genes have been revealed to constitute a multigene family, the Reg family, which consists of three subtypes (types I, II, III) based on the primary structures of the encoded proteins of the genes. We have isolated three types of mouse Reg family gene (Reg I. Reg II, Reg IIIa, Reg III beta and Reg III gamma) [Unno et al. (1993) J. Biol. Chem. 268, 15 974-15 982; Narushima et al. (1997) Gene 185, 159-168]. In the present study, by Southern blot analysis of a mouse bacterial artificial chromosome clone containing the five Reg family genes in combination with PCR cloning of every interspace fragment between adjacent genes, the Reg family genes were mapped to a contiguous 75 kb region of the mouse genome according to the following order: 5'-Reg III beta-Reg III alpha-Reg II-Reg I-REg III gamma-3;. In the process of ordering the genes, we sequenced the 6.8 kb interspace fragment between Reg III beta and Reg III alpha and encountered a novel type III Reg gene, Reg III delta. This gene is divided into six exons spanning about 3 kb, and encodes a 175 amino acid protein with 40-52% identity with the other five mouse Reg (regenerating gene product) proteins. Reg III delta was expressed predominantly in exocrine pancreas, but not in normal islets, hyperplastic islets, intestine or colon, whereas both Reg I and Reg II were expressed in hyperplastic islets and Reg III alpha, Reg III beta and Reg III gamma were expressed strongly in the intestinal tract. Possible roles of Reg III delta and the widespread occurrence of the Reg IIIb gene in mammalian genomes are discussed. (C) 2000 Elsevier Science B.V. All rights reserved.