Plac1 (placenta-specific 1) is essential for normal placental and embryonic development

Plac1 is a recently identified, X‐linked gene whose expression is restricted primarily to cells of the trophoblast lineage. It localizes to a chromosomal locus previously implicated in placental growth. We therefore sought to determine if Plac1 is necessary for placental and embryonic development by examining a mutant mouse model. Plac1 ablation resulted in placentomegaly and mild intrauterine growth retardation (IUGR). At E16.5, knockout (KO) and heterozygous (Het) placentae of the Plac1‐null allele inherited from the mother (X^m?X) weighed approximately 100% more than wildtype (WT) placentae, whereas the corresponding embryos weighed 7–12% less. Histologically, Plac1 mutants exhibited an expanded spongiotrophoblast layer that invaded the labyrinth. By contrast, Het placentae that inherited the null allele from the father (XX^p?) exhibited normal growth and were histologically indistinguishable from WT placentae, consistent with paternal imprinting of Plac1. When examined across gestation, WT and X^m?X placental weights peaked at E16.5 and decreased slightly thereafter. KO placentae (X^m?X^p? and X^m?Y), however, continued to increase in weight after E16.5, consistent with a functional role for the paternal Plac1 allele. Subsequent analysis confirmed that the paternal allele partially escapes complete X‐inactivation and thus contributes to placental growth regulation. Additionally, although male Plac1 KO mice can survive, they exhibit decreased viability as a consequence of events occurring late in gestation or shortly after birth. Thus, Plac1 is a paternally imprinted, X‐linked gene essential for normal placental and embryonic development.Mol. Reprod. Dev. 79: 564‐572, 2012. © 2012 Wiley Periodicals, Inc.