Showing papers in "Public Administration in 1972"

Three Blind Mice

Abstract: During embryogenesis, in all mammals, the eyelids grow across the eye anterior, fuse together, and subsequently reopen. This process is essential for proper eye development. ADAM17 is a Zn metalloprotease that has a role in cleaving numerous proteins including growth factors involved in EGFR signaling, a molecular pathway essential for cell migration. Mice with mutations in genes encoding ADAM17, EGFR, and EGFR ligands exhibit defects in embryonic eyelid closure. Recently, woe (wavy with open eyelids) mice, also exhibiting defects in embryonic eyelid closure, were identified. Genetic analysis of woe mice identified a mutation in ADAM17 leading to three different ADAM17 mutant proteins. Two of these mutant proteins were catalytically inactive; however, the third mutant protein exhibited normal ADAM17 catalytic activity. Further molecular analysis showed that this catalytically active mutant protein exhibited T265M substitution and was expressed at very low levels. The T265 residue is within the ADAM17 Zn catalytic domain (215–473 aa). The T265M mutant protein exhibits normal ADAM17 catalytic activity most likely because T265 residue is not in the Zn active site. The Saint Joan Antida SMART Team modeled ADAM17’s catalytic core using 3-D printing technology. In addition SMART Team identified the location of the T265 amino acid residue within the catalytic core and its position relative to the active site. A better understanding of which amino acids are essential for the ADAM17 catalytic function will ultimately lead to a better understanding of ADAM17-mediated EGFR pathway and the role of this pathway in cell migration and organ development. The SMART Team Program (Students Modeling A Research Topic) is funded by a grant from NIH-SEPA 1R25OD010505-01 from NIH-CTSA UL1RR031973. Figure 2.