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Placental growth retardation due to loss of imprinting of Phlda2

Salas, Martha, John, Rosalind Margaret ORCID:, 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: 27 Oct 2022 08:47

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