FIG. 7.

Model for genotype-phenotype correlation on distal Chr 7. The analyses of mutant mice carrying the deletion alleles IC2KO and DelTel7 reveal new genetic effects on distal Chr 7. The columns (A to F) represent mice of different genotypes on Chr 7, drawn schematically with a focus on the epigenetic status of IC1 and IC2 on the maternal (mat; black) and paternal (pat; white) homologues. The allelic expression levels of the ncRNA Kcnq1ot1 and several protein-coding genes under its regulation (distal MEGs) are shown for each genotype, as is the observed phenotype. Epigenetic imprinting at IC1 has not been analyzed in DelTel7/DelTel7 preimplantation embryos (F; shaded circles), but normal imprinting of IC1 is observed in animals A to E. Our results with the DelTel7 allele (C and D) confirm the independent epigenetic function of IC1 on Chr 7 in the absence of the entire distal domain. DelTel7 also gives a new imprinted embryonic phenotype upon maternal transmission (D). This phenotype is fully rescued by a paternal IC2KO (E), demonstrating that all of the developmentally required genes normally expressed from the maternal Chr 7 (as in animals A to C) are under IC2-mediated silencing on the paternal Chr 7.