PARENTAL IMPRINTING OF AN IGF-2 TRANSGENE

As a consequence of parental imprinting in mice, the paternal allele e ncoding insulin-like growth factor-II (IGF-II) is expressed, whereas t he maternal allele is silent in most tissues. To examine whether cis-a cting sequences involved in imprinting are located in the vicinity of the Igf-2 gene, we have constructed mouse transgenic lines and studied the expression of a 30 kb rat Igf-2 transgene, in which the coding re gion has been replaced with the lacZ reporter sequence. Chromatin posi tion effects and/or absence of long-range regulatory elements seem to have affected tissue-specific expression in the transgenic mice. Howev er, in one of six expressing lines, staining of embryos for beta-galac tosidase activity was detected in a minor subset of tissues normally t ranscribing the endogenous homolog, but only when the transgene was tr ansmitted paternally. This transgene was integrated into mouse chromos ome 19, which is apparently free of imprinted loci. Although the possi bility that the Igf-2 transgene was inserted into an as yet unidentifi ed imprinted locus is discussed, a more likely interpretation of our r esults is that the transgene carries at least a portion of its own imp rinting signal, because it consists of the genomic sequences of a locu s already known to be imprinted and maintains the correct imprinting m ode. (c) 1993 Wiley-Liss, Inc.