{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T22:50:19Z","timestamp":1784328619948,"version":"3.55.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,12,23]]},"abstract":"<jats:p>\n                    The hyperglycemia of maternal diabetes suppresses the glucose transporter-1 (GLUT1) facilitative glucose transporter 49\u201366% in preimplantation embryos. Glucose uptake is reduced and apoptosis is activated. We hypothesized that the reduction of embryonic GLUT1 may play a key role in the malformations of diabetic embryopathy. Therefore, we produced GLUT1-deficient transgenic mice [i.e., antisense-GLUT1 (GT1AS)] to determine whether GLUT1 deficiency alone could reproduce the growth defects. Early cell division of fertilized mouse eggs injected with GT1AS was markedly impaired,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001 vs. controls. Two populations of preimplantation embryos obtained from GT1AS \u00d7 GT1AS heterozygote matings exhibited reduction of the 2-deoxyglucose uptake rate: one by 50% (presumed heterozygotes,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001 vs. control) and the other by 95% (presumed homozygotes,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001 vs. heterozygotes). Embryonic GLUT1 deficiency in the range reported with maternal diabetes was associated with growth retardation and developmental malformations similar to those described in diabetes-exposed embryos: intrauterine growth retardation (31.1%), caudal regression (9.8%), anencephaly with absence of the head (6.6%), microphthalmia (4.9%), and micrognathia (1.6%). Reduced body weight (small embryos, &lt;70% of the nontransgenic body weight) was accompanied by other malformations and a 56% reduction of GLUT1 protein,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001 vs. nonsmall embryos (body weight \u226570% normal). The heart, brain, and kidneys of embryonic day 18.5 GT1AS embryos exhibited 24\u201351% reductions of GLUT1 protein. The homozygous GT1AS genotype was lethal during gestation. Reduced embryonic GLUT1 was associated with the appearance of apoptosis. Therefore, GLUT1 deficiency may play a role in producing embryonic malformations resulting from the hyperglycemia of maternal diabetes. Late gestational macrosomia was absent, apparently requiring a different mechanism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2536196100","type":"journal-article","created":{"date-parts":[[2003,12,23]],"date-time":"2003-12-23T12:58:11Z","timestamp":1072184291000},"page":"15613-15618","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":103,"title":["Glucose transporter-1-deficient mice exhibit impaired development and deformities that are similar to diabetic embryopathy"],"prefix":"10.1073","volume":"100","author":[{"given":"Charles W.","family":"Heilig","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; Harvard Medical School, Boston, MA 02115; University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Henry Ford Health Sciences Center, Detroit, MI 48202; University of Michigan Medical School, Ann Arbor, MI 48109; and Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Saunders","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; Harvard Medical School, Boston, MA 02115; University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Henry Ford Health Sciences Center, Detroit, MI 48202; University of Michigan Medical School, Ann Arbor, MI 48109; and Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Frank C.","family":"Brosius","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; Harvard Medical School, Boston, MA 02115; University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Henry Ford Health Sciences Center, Detroit, MI 48202; University of Michigan Medical School, Ann Arbor, MI 48109; and Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelle","family":"Moley","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; Harvard Medical School, Boston, MA 02115; University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Henry Ford Health Sciences Center, Detroit, MI 48202; University of Michigan Medical School, Ann Arbor, MI 48109; and Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Heilig","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; Harvard Medical School, Boston, MA 02115; University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Henry Ford Health Sciences Center, Detroit, MI 48202; University of Michigan Medical School, Ann Arbor, MI 48109; and Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Baggs","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; Harvard Medical School, Boston, MA 02115; University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Henry Ford Health Sciences Center, Detroit, MI 48202; University of Michigan Medical School, Ann Arbor, MI 48109; and Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiRong","family":"Guo","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; Harvard Medical School, Boston, MA 02115; University of Rochester School of Medicine and Dentistry, Rochester, NY 14642; Henry Ford Health Sciences Center, Detroit, MI 48202; University of Michigan Medical School, Ann Arbor, MI 48109; and Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Conner","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205; 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