Differential expression of reg-I and reg-II genes during aging in the normal mouse.

A cDNA termed reg (for regenerating gene) has been isolated from a rat pancreatic DNA library. Reg expression has been shown to correlate with changes in beta cell mass and function. This finding has been recently challenged by studies showing a non-beta-cell-dependent regulation of reg expression. All studies to date, however, have neglected the fact that two nonallelic reg genes (reg-I and reg-II) exist in several species. In studying the regulation of each individual copy gene, we investigated reg-I and -II gene expression in a naturally occurring modification of beta-cell physiology: normal aging. RNA was isolated from individual pancreata of 1-, 3-, 9-, 20-, and 30-month-old C57BL/6J mice (n > or = 3 per group) and subjected to slot-blot analysis using homologous probes for reg-I, reg-II, insulin, and elastase-I. A progressive age-dependent decrease in total reg mRNA levels (reg-I and -II) was detected. At 30 months of age, total reg mRNA levels were approximately 45% of the level detected in 1-month-old mice (p = .01). This paralleled the decrease in insulin mRNA levels (p = .01), which fell below 50%; by contrast, mRNA levels for elastase-I increased with age (p = .05). Analysis of RNA isolated from purified islets did not reveal any mRNA for reg, suggesting that in the normal mouse, reg is primarily a product of the exocrine pancreas. Reg mRNA were detectable in RNA extracts from stomach, duodenum, and small intestine. By hybridization of total pancreatic RNA with oligonucleotide probes which specifically recognize reg-I or reg-II sequences, we show that reg-I mRNA levels declined with age (p = .001) while reg-II mRNA levels remained unchanged. These data demonstrate that in mouse pancreas the two nonallelic reg genes are differentially expressed during aging and that the decrease in reg-I mRNA levels parallels the decrease in insulin gene expression. Differential regulation of reg-I and reg-II genes may explain the presence of conflicting data in the current literature.