Abstract
The biological impetus for gene dosage and allele specificity of mammalian imprinted genes is not fully understood. To address this, we generated and analyzed four sets of mice from a single breeding scheme with varying allelic expression and gene dosage of the Peg3 domain. The mutants with abrogation of the two paternally expressed genes, Peg3 and Usp29, showed a significant decrease in growth rates for both males and females, while the mutants with biallelic expression of Peg3 and Usp29 resulted in an increased growth rate of female mice only. The mutant cohort with biallelic expression of Peg3 and Usp29 tended to have greater numbers of pups compared to the other genotypes. The mutants with switched active alleles displayed overall similar phenotypes to the wild type, but did show some differences in gene expression, suggesting potential non-redundant roles contributed by the maternal and paternal alleles. Overall, this study demonstrates a novel in vivo approach to investigate the allele and dosage specificity of mammalian imprinted domains.
Highlights
IntroductionThe majority of autosomal genes have two functional copies, which are contributed by two parents
In placental mammals, the majority of autosomal genes have two functional copies, which are contributed by two parents
We characterized the allele and dosage specificity associated with the Peg3 domain by using two mutant alleles targeting the Peg3-DMR and the alternative U1 promoter
Summary
The majority of autosomal genes have two functional copies, which are contributed by two parents. A very small subset of genes has only one functional copy due to genomic imprinting, by which one allele is inactivated by epigenetic mechanisms [1,2,3]. This mono-allelic expression or single gene dosage driven by genomic imprinting has been functionally selected and preserved during the evolution of eutherian mammals [1,2,3]. The actual biological reasons for the allele and dosage specificity associated with each imprinted gene have not been well understood so far
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