| First Author | Freschi A | Year | 2018 |
| Journal | PLoS Genet | Volume | 14 |
| Issue | 2 | Pages | e1007243 |
| PubMed ID | 29470501 | Mgi Jnum | J:258742 |
| Mgi Id | MGI:6147499 | Doi | 10.1371/journal.pgen.1007243 |
| Citation | Freschi A, et al. (2018) Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice. PLoS Genet 14(2):e1007243 |
| abstractText | 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. |
