Mouse ribosomal RNA genes contain multiple differentially regulated variants

Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documentaed in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e independent of other rDNA variants) and tissue-specifically, have not been successful. We report here the molecuar cloning and characterization of seven mouse rDNA variants (v-rDNA). The identification of these v-rDNA was based on restriction fragment length polymorphisms (RFLPs) which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs) in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNA are expressed in all tissues (constitutively active) two are expressed in some tissues (selectively active), and two are not expressed (silent). These expression profiles were observed in six individuals from three mouse variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.