Dosage-Sensitive Requirement for Mouse Dll4 in Artery Development
Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH COMMUNICATION Dosage-sensitive requirement 2000), which were also observed, to a lesser degree, in Hey1/Hey2 double mutants, the putative downstream for mouse Dll4 targets of Notch signaling (Fischer et al. 2004). Here we in artery development show, in contrast, that the Dll4 ligand alone is required in a dosage-sensitive manner for normal arterial pattern- António Duarte,1,5 Masanori Hirashima,3,5,6 ing in development. Rui Benedito,1 Alexandre Trindade,1 The Dll4 gene was inactivated by targeted disruption 1 2 1 in embryonic stem (ES) cells. The targeting vector was Patrícia Diniz, Evguenia Bekman, Luís Costa, designed to replace the initiation codon and the first 2 3,4,7 Domingos Henrique, and Janet Rossant three coding exons with the -galactosidase (lacZ) re- porter gene (Fig. 1A). Electroporation of R1 ES cells with 1CIISA, Faculdade de Medicina Veterina´ria, 1300-0-477 the targeting vector followed by G418 selection resulted Lisboa, Portugal; 2Instituto de Medicina Molecular, Faculdade in the derivation of four correctly gene-targeted ES cell de Medicina, 1649-9-028 Lisboa, Portugal; 3Samuel Lunenfeld lines. Chimeric mice were generated by aggregation be- Research Institute, Mount Sinai Hospital, Toronto, Ontario, tween Dll4+/− ES cells and ICR host embryos. When Canada M5G1X5; 4Department of Molecular and Medical crossed with wild-type ICR females, five male chimeras Genetics, University of Toronto, Toronto, Ontario, produced F1 agouti pups at 100% frequency. Genotyping Canada M5S 1A8 of F1 agouti mice by Southern blotting or polymerase +/− Involvement of the Notch signaling pathway in vascular chain reaction (PCR; Fig.
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