Plac1 (Placenta-specific 1) Is Widely Expressed during Fetal Development and Is Associated with a Lethal Form of Hydrocephalus

BACKGROUNDPlac1 is an X-linked gene essential for normal placental development. Plac1 ablation is associated with placentomegaly and intrauterine growth retardation. Additionally, Plac1-null mice exhibit reduced postnatal viability. This study was conducted as part of our ongoing examination of the postnatal phenotype associated with Plac1 ablation. METHODSPlac1 was deleted in murine embryonic stem cells and bred against a C57BL/6 background. Mutant mice were genotyped using a polymerase chain reaction-based strategy. Embryonic Plac1 expression was assessed by quantitative real-time polymerase chain reaction, in situ hybridization, and -galactosidase expression. RESULTSA total of 20% of the surviving Xm-Y (knockout) males as well as 10-15% of the Xm-X females (mutant maternal allele) developed lethal hydrocephalus at 4-8 weeks. By contrast, XXp- hets (paternal null allele) did not. Plac1 mRNA expression was detected in the fetal brain that markedly decreased after birth. Plac1 mRNA expression localized to the hindbrain and lateral ventricles of wild-type embryos. Additionally, Plac1 expression was observed throughout the fetus including the fetal lungs, kidney, intestine, liver, and heart. Embryonic Plac1 expression was paternally imprinted with partial escape of the paternal allele from complete inactivation. The Plac1 protein localized to the apical surface of the epithelial cells lining the developing airways of the lung and proximal renal tubules, consistent with its localization in the differentiated syncytiotrophoblast. CONCLUSIONPlac1 is expressed in the brain in a developmentally regulated manner and its absence is linked to increased risk for hydrocephalus. It is also widely expressed in fetal tissues expanding the existing paradigm to include direct tissue-specific roles during development. (c) 2013 Wiley Periodicals, Inc.