Genomic imprinting is essential for mammalian development. Curiously, elements that regulate genomic imprinting, the imprinting control regions (ICRs), often diverge across species. To understand whether the diverged ICR sequence plays a species-specific role at the H19/insulin-like growth factor 2 (Igf2) imprinted locus, we generated a mouse in which the human ICR (hIC1) sequence replaced the endogenous mouse ICR. We show that the imprinting mechanism has partially diverged between mouse and human, depending on the parental origin of the hIC1 in mouse. We also suggest that our mouse model is optimal for studying the imprinting disorders Beckwith–Wiedemann syndrome when hIC1 is maternally transmitted, and Silver–Russell syndrome when hIC1 is paternally transmitted
