title: Strain-dependent developmental relaxation of imprinting of an endogenous mouse gene, Kvlqt1.
abstract: Genomic imprinting is an epigenetic modification of the gamete or zygote leading to parental origin-specific differential expression of the two alleles of a gene in somatic cells of the offspring. We previously reported that the human KVLQT1 gene is imprinted and disrupted in patients with germline balanced chromosomal rearrangements and Beckwith-Wiedemann syndrome. In human, the gene is imprinted in most fetal tissues except the heart, and KVLQT1 is part of a 1-Mb cluster of imprinted genes on human chromosome 11p15. 5. We sought to determine whether the mouse Kvlqt1 gene is imprinted, by performing interspecific crosses of 129/SvEv mice with CAST/Ei (Mus musculus castaneus). We identified a transcribed polymorphism that distinguishes the two parental alleles in F1 offspring. Examination of embryonic, neonatal, and postnatal tissues revealed that Kvlqt1 is imprinted in mouse early embryos, in both female 129 x male CS and female CS x male 129 offspring, with preferential expression of the maternal allele, like the human homologue. Surprisingly, imprinting was developmentally relaxed, and the developmental stage and tissue specificity of relaxation of imprinting was strain-dependent. To our knowledge, this is the first example of an endogenous gene that shows strain-dependent developmental relaxation of imprinting.
authors.affiliation: Graduate Program in Cellular and Molecular Medicine, Graduate Program in Human Genetics, Department of Medicine, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: M A
authors.initials: MA
authors.lastname: Hemann
authors.forename: M P
authors.initials: MP
authors.lastname: Lee
authors.forename: A P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D011247:Pregnancy; D012313:RNA / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D017931:DNA Primers; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C496910:Kcnq1 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012313:RNA