title: Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1.
abstract: The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for embryonic development in mammals. Mutations in the human JAGGED1 ( JAG1 ) gene, which encodes a ligand for the Notch family of transmembrane receptors, cause the autosomal dominant disorder Alagille syndrome. We have examined the in vivo role of the mouse Jag1 gene by creating a null allele through gene targeting. Mice homozygous for the Jag1 mutation die from hemorrhage early during embryogenesis, exhibiting defects in remodeling of the embryonic and yolk sac vasculature. We mapped the Jag1 gene to mouse chromosome 2, in the vicinity of the Coloboma ( Cm ) deletion. Molecular and complementation analyses revealed that the Jag1 gene is functionally deleted in the Cm mutant allele. Mice heterozygous for the Jag1 null allele exhibit an eye dysmorphology similar to that of Cm /+ heterozygotes, but do not exhibit other phenotypes characteristic of Cm /+ mice or of humans with Alagille syndrome. These results establish the phenotype of Cm /+ mice as a contiguous gene deletion syndrome and demonstrate that Jag1 is essential for remodeling of the embryonic vasculature.
authors: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609-1500, USA.
authors: Y
authors: Y
authors: Xue
authors: X
authors: X
authors: Gao
authors: C E
authors: CE
authors: Lindsell
authors: C R
authors: CR
authors: Norton
authors: B
authors: B
authors: Chang
authors: C
authors: C
authors: Hicks
authors: M
authors: M
authors: Gendron-Maguire
authors: E B
authors: EB
authors: Rand
authors: G
authors: G
authors: Weinmaster
authors: T
authors: T
authors: Gridley
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D002135:Calcium-Binding Proteins; D002874:Chromosome Mapping; D004622:Embryo, Mammalian / Q000503:physiopathology; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D005313:Fetal Death / Q000235:genetics*; D017353:Gene Deletion; D006579:Heterozygote; D006720:Homozygote; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009154:Mutation; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011506:Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins