دورية أكاديمية
Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice
| العنوان: | Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice |
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| المؤلفون: | Freschi, A., Hur, S.K., Valente, F.M., Ideraabdullah, F.Y., Sparago, A., Gentile, M.T., Oneglia, A., Di Nucci, D., Colucci-D'Amato, L., Thorvaldsen, J.L., Bartolomei, M.S., Riccio, A., Cerrato, F. |
| المصدر: | PLoS Genetics, 14(2) |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2018 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Mice, Inbred C57BL, Female, Pregnancy, Animals, Genomic Imprinting, Mouse Embryonic Stem Cells, RNA, Long Noncoding, Inbred BALB C, Cells, Cultured, Humans, Mutation, Male, Phenotype, Mosaicism, Transgenic, Insulin-Like Growth Factor II, Growth Disorders, Organ Specificity |
| الوصف: | Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures. Due to structural differences between human and mouse, the mechanisms by which mutations of the H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined. To address this issue, we previously generated a mouse line carrying a humanized IC1 (hIC1) and now replaced the wildtype with a mutant IC1 identified in the overgrowth-associated Beckwith-Wiedemann syndrome. The new humanized mouse line shows pre/post-natal overgrowth on maternal transmission and pre/post-natal undergrowth on paternal transmission of the mutation. The mutant hIC1 acquires abnormal methylation during development causing opposite H19/Igf2 imprinting defects on maternal and paternal chromosomes. Differential and possibly mosaic Igf2 expression and imprinting is associated with asymmetric growth of bilateral organs. Furthermore, tissue-specific imprinting defects result in deficient liver- and placenta-derived Igf2 on paternal transmission and excessive Igf2 in peripheral tissues on maternal transmission, providing a possible molecular explanation for imprinting-associated and phenotypically contrasting growth disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/vzdy-k510Test; https://cdr.lib.unc.edu/downloads/6d570565c?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/6d570565cTest |
| DOI: | 10.17615/vzdy-k510 |
| الإتاحة: | https://doi.org/10.17615/vzdy-k510Test https://cdr.lib.unc.edu/downloads/6d570565c?file=thumbnailTest https://cdr.lib.unc.edu/downloads/6d570565cTest |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.291099CC |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/vzdy-k510 |
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