Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith–Wiedemann and Simpson–Golabi–Behmel syndromes
Copyright policy )Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith–Wiedemann and Simpson–Golabi–Behmel syndromes
In mice, the imprintedIgf2gene (expressed from the paternal allele), which encodes a growth-promoting factor (IGF-II), is linked closely to the reciprocally imprintedH19locus on chromosome 7. Also imprinted (expressed from the maternal allele) is theIgf2rgene on chromsome 17 encoding the type 2 IGF receptor that is involved in degradation of excess IGF-II. Double mutant embryos carrying a deletion around theH19region and also a targetedIgf2rallele, both inherited maternally, have extremely high levels of IGF-II (7- and 11-fold higher than normal in tissues and serum, respectively) as a result of biallelicIgf2expression (imprint relaxation by deletion ofH19-associated sequence) in combination with lack of the IGF2R-mediated IGF-II turnover. This excess of IGF-II causes somatic overgrowth, visceromegaly, placentomegaly, omphalocele, and cardiac and adrenal defects, which are also features of the Beckwith–Wiedemann syndrome (BWS), a genetically complex human disorder associated with chromosomal abnormalities in the 11p15.5 region where theIGF2gene resides. In addition, the double mutant mouse embryos exhibit skeletal defects and cleft palate, which are manifestations observed frequently in the Simpson–Golabi–Behmel syndrome, another overgrowth disorder overlapping phenotypically, but not genetically, with BWS.
- University of Chicago United States
- King’s University United States
- College of New Jersey United States
Heart Defects, Congenital, Male, Beckwith-Wiedemann Syndrome, Gene Expression Regulation, Developmental, Bone and Bones, Cleft Palate, Disease Models, Animal, Mice, Fetus, Insulin-Like Growth Factor II, Adrenal Cortex, Animals, Humans, Abnormalities, Multiple, Female, Eye Abnormalities, Cyclin-Dependent Kinase Inhibitor p57, Fetal Death, Crosses, Genetic, Hernia, Umbilical
Heart Defects, Congenital, Male, Beckwith-Wiedemann Syndrome, Gene Expression Regulation, Developmental, Bone and Bones, Cleft Palate, Disease Models, Animal, Mice, Fetus, Insulin-Like Growth Factor II, Adrenal Cortex, Animals, Humans, Abnormalities, Multiple, Female, Eye Abnormalities, Cyclin-Dependent Kinase Inhibitor p57, Fetal Death, Crosses, Genetic, Hernia, Umbilical
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