Imprinted expression of the non-coding RNA, H19 (H19, imprinted maternally expressed transcript), and Igf2 (insulin-like growth factor 2) loci are dependent upon the imprinting control region (ICR or Rr27) that coordinates the reciprocal maternal/paternal expression of H19 and Igf2 by controlling access to shared enhancers. The ICR is located downstream of Igf2 and -2 to -4 kb upstream of the H19 transcriptional start site; it contains four CTCF binding sites and multiple CpG regions. Hypermethylation of the paternal allele blocks binding of the insulator protein CTCF. Hypomethylation of the maternal allele allows binding of CTCF to the four CTCF binding sites. CTCF binding blocks Igf2 access to the shared enhancers 3' of H19. Paternal transmission of this region results in the expression of Igf2 and repression of H19, maternal transmission results in the reciprocal, expression of H19 and repression of Igf2. Aberrant expression of H19/Igf2 is associated with Beckwith-Wiedeman Syndrome.
 The ICR region of the H19ICR-8nrCG mouse is altered to delete 8 CpGs (16% of CpGs) outside of the CTCF binding sites without altering the size of the ICR. The deletion results in loss of repression of the paternal H19, but does not alter methylation at the H19 ICR or promoter. Igf2 expression is unchanged. These deletions do not alter imprinting of the maternal H19/Igf2 alleles. Mice homozygous for the H19ICR-8nrCG allele are viable and fertile. This strain may be useful for studying the role of the imprinting control region in the chromatin interactions and epigenetics of H19/Igf2 imprinting.

The H19ICR-8nrCG mutant allele carries a deletion of 8 CpGs in the imprinting control region (ICR or Rr27) resulting in loss of repression of the paternal H19 imprinting gene. This strain may be useful for studying role of the imprinting control region in the chromatin interactions and epigenetics of H19/Igf2 imprinting.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.