Scientific background: |
DLL3(DELTA-LIKE 3) also known as DELTA, DROSOPHILA, HOMOLOG OF, is a protein which in humans is encoded by the DLL3 gene. This gene encodes a member of the delta protein ligand family. This family functions as Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. Mutation in the mouse delta-like 3 gene (Dll3), which is homologous to the Notch-ligand delta in Drosophila, results in the mouse 'pudgy' phenotype. The human DLL3 gene was identified within a critical interval, mapped in 2 consanguineous Arab-Israeli and Pakistani SCDO1 pedigrees, of 7.8 cM at 19q13.1-q13.3 between D19S570 and D19S908 (Bulman et al., 2000). Dunwoodie et al. (1997) presented results suggesting that mouse Dll3 may complement the function of other delta homologs during early pattern formation in the mouse embryo. In humans, the fact that mutations in genes required for oscillation, such as DLL3, result in abnormal segmentation of the vertebral column suggests that the segmentation clock also acts during human embryonic development. This residue is highly conserved in Delta proteins from Drosophila to humans, and the substitution of a charged polar for a nonpolar residue may disrupt the conformation of the DLL3 protein. |
References: |
1. Bulman, M. P., Kusumi, K., Frayling, T. M., McKeown, C., Garrett, C., Lander, E. S., Krumlauf, R., Hattersley, A. T., Ellard, S., Turnpenny, P. D. Mutations in the human delta homologue,DLL3, cause axial skeletal defects in spondylocostal dysostosis.Nature Genet. 24: 438-441, 2000.
2. Dunwoodie, S. L., Henrique, D., Harrison, S. M., Beddington, R. S. P. Mouse Dll3: a novel divergent delta gene which may complement the function of other delta homologues during early pattern formation in the mouse embryo. Development 124: 3065-3076, 1997.
3. Kusumi, K., Sun, E. S., Kerrebrock, A. W., Bronson, R. T., Chi, D.-C., Bulotsky, M. S., Spencer, J. B., Birren, B. W., Frankel, W. N., Lander, E. S. The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries.Nature Genet. 19: 274-278, 1998.
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