title: Transgene insertion in intronic sequences of Mdga2 gene shows methylation in an imprinted manner in an Acrodysplasia (Adp) mouse line.
abstract: The Acrodysplasia (Adp) mutation arises from the insertion of a transgene containing a mouse metallothionein-promoted bovine papilloma virus and human growth hormone-releasing factor gene. Although the transgene is not expressed, mice that are hemizygous for the transgene show skull and paw deformities when the progeny receive the transgene paternally. To elucidate the molecular mechanisms underlying the mutant phenotype and the modified transmission pattern of the Adp phenotype, a junctional fragment around the transgene integration site was cloned. The transgene was inserted into the intronic sequences between exon 3 and exon 4 of the Mdga2 gene and the degree of methylation of the transgene and the severity of the phenotype were reciprocally related in that the transgene was highly or under methylated in normal and deformed mice, respectively. Thus, methylation of the transgene appears to regulate phenotypic expression and imprinting of Adp.
authors.affiliation: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Suzuki
authors.forename: Davor
authors.initials: D
authors.lastname: Solter
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001483:Base Sequence; D052688:Bovine papillomavirus 1 / Q000235:genetics; D003001:Cloning, Molecular; D019175:DNA Methylation; D004413:Dysostoses / Q000235:genetics*; D005091:Exons / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics*; D056426:Genetic Loci; D018392:Genomic Imprinting; D008607:Intellectual Disability / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics*; D019076:Transgenes
chemical_list: D058851:GPI-Linked Proteins; C571222:MDGA2 protein, mouse; D019006:Neural Cell Adhesion Molecules