Rescue of the T-associated maternal effect in mice carrying null mutations in Igf-2 and Igf2r, two reciprocally imprinted genes

Abstract

In mice, only the paternal allele of the Igf2 gene, encoding insulin-like growth factor II (IGF-II) is expressed due to parental imprinting. Interestingly, the Igf2r gene, which encodes one of the two known receptors (IGF2R) to which IGF-II binds with high affinity is also subject to imprinting, but in a reciprocal fashion. This observation raises the possibility that imprinting of these loci serves to regulate the ratios of the gene products, since IGF2R provides a mechanism for IGF-II turnover. To test this hypothesis, we crossed mice mutant for Igf-2 with animals carrying the Thp chromosomal deletion, which encompasses the Igf2r locus. Inheritance of the Thp chromosome through the maternal germline results in a dominant lethal maternal effect (Tme). However, as we show here, Thp/+ embryos that inherit the Thp maternally are variably rescued to birth if they also lack IGF-II. Based on these data, the Tme phenotype can be viewed as a dominant effect resulting from an overabundance of IGF-II.