Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional Adrenomedullin gene.
Adrenomedullin, a recently identified potent vasodilator, is expressed widely and has been suggested to have functions ranging from reproduction to blood pressure regulation. To elucidate these functions and define more precisely sites of Adm expression, we replaced the coding region of the Adm gene in mice with a sequence encoding enhanced green fluorescent protein while leaving the Adm promoter intact. We find that Adm(-/-) embryos die at midgestation with extreme hydrops fetalis and cardiovascular abnormalities, including overdeveloped ventricular trabeculae and underdeveloped arterial walls. These data suggest that genetically determined absence of Adm may be one cause of nonimmune hydrops fetalis in humans.
Caron
K M
KM
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
Smithies
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D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D053607:Adrenomedullin; D000818:Animals; D001011:Aorta / Q000196:embryology / Q000473:pathology; D002339:Carotid Arteries / Q000196:embryology / Q000473:pathology; D002678:Chimera; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000235:genetics* / Q000473:pathology; D005318:Fetal Heart / Q000002:abnormalities* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D017930:Genes, Reporter; D005838:Genotype; D005865:Gestational Age; D049452:Green Fluorescent Proteins; D006352:Heart Ventricles / Q000196:embryology / Q000473:pathology; D015160:Hydrops Fetalis / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D008164:Luminescent Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D053607:Adrenomedullin