The serine protease inhibitor Alpha- 1 -antitrypsin (Alpha- 1 -AT) is synthesized primarily in the liver, then secreted into the blood where it is important in the physiological regulation of neutrophil elastase. In mice, alpha 1 -AT is encoded by a small multigene family of 2-4 functional members. Alpha 1 -AT expression is regulated in mammals in a developmentally and tissue-specific manner. This gene family therefore represents an excellent model system with which to study important regulatory factors which can control the tissue and temporal expression of mammalian genes. We have defined cis- and trans- acting elements which are important for expression of an Alpha 1-AT gene in cultured cells are necessary and sufficient to ensure tissue-specific and temporally correct expression in vivo. To carry out this analysis, we propose to introduce test constructs of the Alpha 1 -AT gene into fertilized mouse eggs and then to implant these eggs into the uteri of pseudopregnant female mice to generate transgenic offspring. An analysis of the DNA sequence elements required for the expression of test genes in transgenic animals will permit an unambiguous assignment of the cis-acting DNA elements required in vivo for tissue-specific and temporal expression of the Alpha 1-AT gene. A primary goal in this work is to develop the methodologies required for the generation and maintenance of transgenic mice. Besides its value to this project, the establishment of this technology within the Liver Center will make similar studies for other Liver Center investigators much simpler, since we could then collaborate or provide training for others requiring this powerful technology.
| Dulyaninova, Natalya G; Ruiz, Penelope D; Gamble, Matthew J et al. (2018) S100A4 regulates macrophage invasion by distinct myosin-dependent and myosin-independent mechanisms. Mol Biol Cell 29:632-642 |
| Kakabadze, Zurab; Kakabadze, Ann; Chakhunashvili, David et al. (2018) Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. Hepatology 67:1956-1969 |
| Rao, Lu; Hülsemann, Maren; Gennerich, Arne (2018) Combining Structure-Function and Single-Molecule Studies on Cytoplasmic Dynein. Methods Mol Biol 1665:53-89 |
| Gong, Zhenwei; Tasset, Inmaculada; Diaz, Antonio et al. (2018) Humanin is an endogenous activator of chaperone-mediated autophagy. J Cell Biol 217:635-647 |
| Kale, Abhijit; Ji, Zhejun; Kiparaki, Marianthi et al. (2018) Ribosomal Protein S12e Has a Distinct Function in Cell Competition. Dev Cell 44:42-55.e4 |
| Caballero, Benjamin; Wang, Yipeng; Diaz, Antonio et al. (2018) Interplay of pathogenic forms of human tau with different autophagic pathways. Aging Cell 17: |
| Akiyama, Matthew J; Agyemang, Linda; Arnsten, Julia H et al. (2018) Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy. BMC Infect Dis 18:74 |
| Willis, Ian M (2018) Maf1 phenotypes and cell physiology. Biochim Biophys Acta Gene Regul Mech 1861:330-337 |
| Wang, Tony Y; Portincasa, Piero; Liu, Min et al. (2018) Mouse models of gallstone disease. Curr Opin Gastroenterol 34:59-70 |
| Hodge, Dayle Q; Cui, Jihong; Gamble, Matthew J et al. (2018) Histone Variant MacroH2A1 Plays an Isoform-Specific Role in Suppressing Epithelial-Mesenchymal Transition. Sci Rep 8:841 |
Showing the most recent 10 out of 451 publications
