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Here we show that matrix metalloproteinase-9 (MMP9) deficiency causes physiological and placental abnormalities in mice, which mimic features of PE. As with the severe cases of this syndrome, which commence early in gestation, MMP9-null mouse embryos exhibit deficiencies in trophoblast differentiation and invasion shortly after implantation, along with intrauterine growth restriction or embryonic death. Reciprocal embryo transfer experiments demonstrated that embryonic MMP9 is a major contributor to normal implantation, but maternal MMP9 also plays a role in embryonic trophoblast development. Pregnant MMP9-null mice bearing null embryos exhibited clinical features of PE as VEGF dysregulation and proteinuria accompanied by preexisting elevated blood pressure and kidney pathology. Thus, our data show that fetal and maternal MMP9 play a role in the development of PE and establish the MMP9-null mice as a much-needed model to study the clinical course of this syndrome.<\/jats:p>","DOI":"10.1073\/pnas.1309561110","type":"journal-article","created":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T23:05:44Z","timestamp":1371510344000},"page":"11109-11114","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":153,"title":["Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction"],"prefix":"10.1073","volume":"110","author":[{"given":"Vicki","family":"Plaks","sequence":"first","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143;"}]},{"given":"Julie","family":"Rinkenberger","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143;"}]},{"given":"Joanne","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143;"}]},{"given":"Margaret","family":"Flannery","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143;"}]},{"given":"Malin","family":"Sund","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}]},{"given":"Keizo","family":"Kanasaki","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}]},{"given":"Wei","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Diabetes Center, University of California, San Francisco, CA 94143; and"}]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030."}]},{"given":"Zena","family":"Werb","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of California, San Francisco, CA 94143;"}]}],"member":"341","published-online":{"date-parts":[[2013,6,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006585"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2004.07.002"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0412.2003.00220.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2010.12.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17987-2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.12.006"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2741\/2249"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.015"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gar033"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.6.1723"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.08.006"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/ob.1996.v175.a74404"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.113.2.437"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0301-2115(96)02484-0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.12.95"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10910"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002020408"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199903)214:3<248::AID-AJA8>3.0.CO;2-N"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0918"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199702)208:2<255::AID-AJA12>3.0.CO;2-2"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051980308"},{"key":"e_1_3_3_22_2","first-page":"253","article-title":"Increased placental antifibrinolytic potential and fibrin deposits in pregnancy-induced hypertension and preeclampsia","volume":"74","author":"Kanfer A","year":"1996","unstructured":"A Kanfer, et al., Increased placental antifibrinolytic potential and fibrin deposits in pregnancy-induced hypertension and preeclampsia. 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