Rescue of the T-associated maternal effect in mice carrying null mutations in Igf-2 and Igf2r, two reciprocally imprinted genes.
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.
Filson
A J
AJ
Department of Genetics and Development, Columbia University, New York, NY 10032.
Louvi
A
A
Efstratiadis
A
A
Robertson
E J
EJ
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D005260:Female; D005313:Fetal Death / Q000235:genetics / Q000517:prevention & control; D005786:Gene Expression Regulation; D005796:Genes; D005804:Genes, Lethal; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains / Q000196:embryology / Q000235:genetics*; D008969:Molecular Sequence Data; D009035:Mothers; D009154:Mutation; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis / Q000235:genetics*; D017384:Sequence Deletion
D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II