Interactions between imprinting effects in the mouse.

Abstract

Mice with uniparental partial or complete disomies for any one of 11 identified chromosomes show abnormal phenotypes. The abnormalities, or imprinting effects, can be attributable to an incorrect dosage of maternal or paternal copies of imprinted gene(s) located within the regions involved. Here we show that combinations of partial disomies may result in interactions between imprinting effects that seemingly independently affect fetal and/or placental growth in different ways or modify neonatal and postnatal imprinting effects. Candidate genes within the regions have been identified. The findings are generally in accord with the "conflict hypothesis" for the evolution of genomic imprinting but do not clearly demonstrate common growth axes within which imprinted genes may interact. Instead, it would seem that any gene that represses or limits embryonic/fetal growth to the advantage of the mother--by any developmental means--will have been subject to evolutionary selection for paternal allele repression. Likewise, any gene that favors embryonic/fetal development at consequent cost to the mother--by any developmental means--will have faced selection for maternal allele repression. The classical Igf2-Igf2r axis may therefore be unique. The findings involve reinterpretation of older imprinting data and consequently revision of the mouse imprinting map.