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Placental growth retardation due to loss of imprinting of Phlda2

Salas, Martha, John, Rosalind Margaret, Saxena, Anjana, Barton, Sheila, Frank, Dale, Fitzpatrick, Galina, Higgins, Michael J. and Tycko, Benjamin 2004. Placental growth retardation due to loss of imprinting of Phlda2. Mechanisms of Development 121 (10) , pp. 1199-1210. 10.1016/j.mod.2004.05.017

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The maternally expressed/paternally silenced genes Phlda2 (a.k.a. Ipl/Tssc3), Slc22a1l, Cdkn1c, Kcnq1, and Ascl2 are clustered in an imprinted domain on mouse chromosome 7. Paternal deletion of a cis-acting differentially methylated DNA element, Kvdmr1, causes coordinate loss of imprinting and over-expression of all of these genes and the resulting conceptuses show intrauterine growth restriction (IUGR). To test the specific contribution of Phlda2 to IUGR in the Kvdmr1-knockout, we crossed Kvdmr1+/− males with Phlda2+/− females. Conceptuses with the (Phlda2+/+; Kvdmr1+/−) genotype showed fetal and placental growth retardation. Restoration of Phlda2 dosage to normal, as occurred in the conceptuses with the (Phlda2−/+; Kvdmr1+/−) genotype, had a marginally positive effect on fetal weights and no effect on post-natal weights, but significantly rescued the placental weights. As we previously reported, loss of Phlda2 expression in the wild-type background (Phlda2−/+; Kvdmr1+/+ genotype) caused placentomegaly. Thus Phlda2 acts as a true rheostat for placental growth, with overgrowth after gene deletion and growth retardation after loss of imprinting. Consistent with this conclusion, we observed significant placental stunting in BAC-transgenic mice that over-expressed Phlda2 and one flanking gene, Slc22a1l, but did not over-express Cdkn1c.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 0925-4773
Last Modified: 04 Jun 2017 06:39

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