Transgene insertion in intronic sequences of Mdga2 gene shows methylation in an imprinted manner in an Acrodysplasia (Adp) mouse line
pmid: 22281501
Transgene insertion in intronic sequences of Mdga2 gene shows methylation in an imprinted manner in an Acrodysplasia (Adp) mouse line
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.
- Max Planck Society Germany
- National University of Singapore Singapore
- National University of Singapore Libraries Singapore
- Nara Women's University Japan
Male, 570, Mdga2, Genomic imprinting, Molecular Sequence Data, 610, Mice, Transgenic, GPI-Linked Proteins, Osteochondrodysplasias, Methylation, Genomic Imprinting, Mice, Insertional mutation, Intellectual Disability, Animals, Transgenes, Cloning, Molecular, Neural Cell Adhesion Molecules, Limb development, Bovine papillomavirus 1, Base Sequence, Dysostoses, Exons, DNA Methylation, Introns, Mutagenesis, Insertional, Genetic Loci
Male, 570, Mdga2, Genomic imprinting, Molecular Sequence Data, 610, Mice, Transgenic, GPI-Linked Proteins, Osteochondrodysplasias, Methylation, Genomic Imprinting, Mice, Insertional mutation, Intellectual Disability, Animals, Transgenes, Cloning, Molecular, Neural Cell Adhesion Molecules, Limb development, Bovine papillomavirus 1, Base Sequence, Dysostoses, Exons, DNA Methylation, Introns, Mutagenesis, Insertional, Genetic Loci
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