Dycaico, M. J., Grant, S. G. N., Felts, K., Nichols, W. S., Geller, S. A., Hager, J. H., Pollard, A. J., Kohler, S. W., Short, H. P., Jirik, F. R., Hanahan, D., Sorge, J. A. (December 1988) Neonatal Hepatitis Induced by Alpha-1-Antitrypsin - a Transgenic Mouse Model. Science, 242 (4884). pp. 1409-1412. ISSN 0036-8075
Abstract
Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of the human alpha 1-antitrypsin (alpha 1-Pi) gene. All of the alpha 1-Pi transgenic mice expressed the human protein in the liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, but particularly in hepatocytes, and was found in serum in tenfold lower concentrations than the M-allele protein. Mice in one lineage carrying the mutant Z allele expressed high levels of human alpha 1-Pi RNA and displayed significant runting (50% of normal weight) in the neonatal period. This lineage was found to have alpha 1-Pi-induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS). The phenotype of mice in the strain expressing high levels of the Z allele is remarkably similar to human neonatal hepatitis, and this strain may prove to be a useful animal model for studying this disease
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer > drugs and therapies organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal |
| CSHL Authors: | |
| Communities: | CSHL labs |
| Depositing User: | Gail Sherman |
| Date: | 9 December 1988 |
| Date Deposited: | 17 Oct 2017 17:19 |
| Last Modified: | 17 Oct 2017 17:19 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/35141 |
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