{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:28:12Z","timestamp":1791275292717,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T00:00:00Z","timestamp":1389571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010DK55615"],"award-info":[{"award-number":["R01\u2010DK55615"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>\n                    Patients with congenital disorder of glycosylation (CDG), type Ib (MPI\u2010CDG or CDG\u2010Ib) have mutations in phosphomannose isomerase\n                    <jats:italic>(MPI)<\/jats:italic>\n                    that impair glycosylation and lead to stunted growth, liver dysfunction, coagulopathy, hypoglycemia, and intestinal abnormalities. Mannose supplements correct hypo\u2010glycosylation and most symptoms by providing man\u2010nose\u20106\u2010P (Man\u20106\u2010P)\n                    <jats:italic>via<\/jats:italic>\n                    hexokinase. We generated viable\n                    <jats:italic>Mpi<\/jats:italic>\n                    hypomorphic mice with residual enzymatic activity comparable to that of patients, but surprisingly, these mice appeared completely normal except for modest (~15%) embryonic lethality. To overcome this lethality, pregnant dams were provided 1\u20132% mannose in their drinking water. However, mannose further reduced litter size and survival to weaning by 40 and 66%, respectively. Moreover, ~50% of survivors developed eye defects beginning around midgestation. Mannose started at birth also led to eye defects but had no effect when started after eye development was complete. Man\u20106\u2010P and related metabolites accumulated in the affected adult eye and in developing embryos and placentas. Our results demonstrate that disturbing mannose metabolic flux in mice, especially during embryonic development, induces a highly specific, unanticipated pathological state. It is unknown whether mannose is harmful to human fetuses during gestation; however, mothers who are at risk for having MPI\u2010CDG children and who consume mannose during pregnancy hoping to benefit an affected fetus\n                    <jats:italic>in utero<\/jats:italic>\n                    should be cautious.\u2014Sharma, V., Nayak, J., DeRossi, C., Charbono, A., Ichikawa, M., Ng, B. G., Grajales\u2010Esquivel, E., Srivastava, A., Wang, L., He, P., Scott, D. A., Russell, J., Contreras, E., Guess, C. M., Krajewski, S., Del Rio\u2010Tsonis, K., Freeze, H. H. Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 1854\u20131869 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-245514","type":"journal-article","created":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T22:40:46Z","timestamp":1389652846000},"page":"1854-1869","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice"],"prefix":"10.1096","volume":"28","author":[{"given":"Vandana","family":"Sharma","sequence":"first","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonamani","family":"Nayak","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"DeRossi","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Charbono","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mie","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobby 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Russell","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Contreras","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherise M.","family":"Guess","sequence":"additional","affiliation":[{"name":"Sanford\u2010Burnham Medical Research Institute (SBMRI) La Jolla California 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