DISRUPTION OF IMPRINTING CAUSED BY DELETION OF THE H19 GENE REGION INMICE

The imprinted H19 gene, which encodes an untranslated RNA, lies at the end of a cluster of Imprinted genes in the mouse. Imprinting of the i nsulin-2 and insulin-like growth factor 2 genes, which lie about 100 k ilobases upstream of H19, can be disrupted by maternal inheritance of a targeted deletion of the H19 gene and its flanking sequence. Animals inheriting the H19 mutation from their mothers are 27% heavier than t hose inheriting It from their fathers. Paternal inheritance of the dis ruption has no effect, which presumably reflects the normally silent s tate of the paternal gene. The somatic overgrowth of heterozygotes for the maternal deletion is attributed to a gain of function of insulin- like growth factor 2, rather than a loss of function of H19.