IGF2R: Sense and Antisense

Robert Lyle
The Netherlands Cancer Institute

We are studying the mechanisms involved in genomic imprinting in the mouse using the mouse insulin-like growth factor type 2 receptor (Igf2r), a maternally expressed gene, as a model.

Work in our lab using YAC transgenic constructs has demonstrated that maternal-specific expression of lgf2r is dependent upon region 2, a CpG-rich region within intron 2 which is methylated on the maternal chromosome (1). In these transgenic experiments, expression of a novel paternally expressed antisense RNA, termed Air (for Antisense Igf2r RNA), was shown to depend upon the unmethylated region 2 on the paternal chromosome.

Region 2 thus acts in cis to repress Igf2r expression. The model we propose is that Igf2r and Air interact by expression competition that may involve the antisense RNA itself.

As a basis for understanding the imprinting mechanism, we have sequenced 138 kb containing Igf2r/Air. This has enabled us to determine the organization of the Air transcript, and the sequence is being used to help identify other features common to imprinted regions of the genome.


  1. Wutz, A., Smrzka, O.W., Schweifer, N., Schellander, K., Wagner, EF, Barlow, D.P. Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389:745-749, 1997.